Acrylonitrile induced cell cycle arrest and apoptosis by promoting the formation of reactive oxygen species in human choriocarcinoma cells.

Acrylonitrile (AN), which is widely utilized in the manufacture of plastics, acrylamide, acrylic fibers, and resins, is also one of main components of cigarette smoke (CS). In this study, we examined the effects of AN on the cell viability and apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cell lines. A cell viability assay confirmed that AN decreased the cell proliferation of JEG-3 and BeWo cells in a dose-dependent manner. Additionally, Western blot assay revealed that protein expression of cyclin D and cyclin E decreased, while protein expression of p21 and p27 increased in response to AN treatment for 48 hr. The changes in reactive oxygen species (ROS) levels in JEG-3 and BeWo cells exposed to AN were also measured by a dichlorofluorescein diacetate (DCFH-DA) assay, which revealed that ROS levels increased in response to AN treatment for 48 hr. Moreover, western blot assay confirmed that AN treatment of JEG-3 and BeWo cells for 4 hr promoted the expression of phosphorylated eukaryotic initiation factor 2 alpha protein (p-eIF2α), C/EBP homologous protein (CHOP) and caspase 12, which are known to be involved in ROS-mediated endoplasmic reticulum stress (ER-stress)-related apoptosis. Overall, the protein expression of p53 and Bax (a pro-apoptosis marker) increased, while the expression of Bcl-xl (an anti-apoptotic marker) decreased and the number of apoptotic cells increased in response to AN treatment for 48 hr. Taken together, these results suggest that AN has the potential to induce apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cells by activating ROS.

Benzo(a)pyrene induced cell cycle arrest and apoptosis in human choriocarcinoma cancer cells through reactive oxygen species-induced endoplasmic reticulum-stress pathway.

Cigarette smoke (CS) contains over 60 well established carcinogens. In this study, we examined the effects of benzo(a)pyrene (B(a)P), a main CS component, on the viability and apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cell lines. An MTT assay confirmed that B(a)P decreased the cell viability of JEG-3 and BeWo cells in a dose-dependent manner. Additionally, Western blot (WB) assay revealed that protein expression of cyclin D and cyclin E decreased, while protein expression of p21 and p27 was increased in response to B(a)P treatment for 48 h. The changes in reactive oxygen species (ROS) levels in JEG-3 and BeWo cells exposed to B(a)P were also measured by a dichlorofluorescein diacetate (DCF-DA) assay, which revealed that ROS levels increased in response to B(a)P treatment for 48 h. WB assay also confirmed that each B(a)P treatment of JEG-3 and BeWo cells for 4 h promoted the expression of phosphorylated eukaryotic initiation factor 2 alpha protein (p-eIF2α) and C/EBP homologous protein (CHOP), which are known to be involved in ROS-mediated endoplasmic reticulum stress (ER-stress) related apoptosis. Overall, the protein expression of Bax (a pro-apoptosis marker) increased, while the expression of Bcl-xl (an anti-apoptotic marker) decreased and the number of apoptotic cells increased in response to B(a)P treatment for 48 h. Taken together, these results suggest that B(a)P has the potential to induce apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cells by increasing the ROS level and simultaneously activating ER-stress.

The role of PPARγ in TBBPA-mediated endocrine disrupting effects in human choriocarcinoma JEG-3 cells.

The goal of the present study was to investigate the action of TBBPA on PPARγ protein expression in vitro in human choriocarcinoma-derived placental JEG-3 cells. We also analyzed TBBPA for its action on placental secretion of progesterone and ß-hCG, cell viability, and apoptosis. Our results showed that after TBBPA treatment at 10 nM and 10 µM, PPARγ protein expression increased in a time-dependent manner until 48 h and then slightly decreased at 72 h but was still above the control level. This alteration in PPARγ protein expression was accompanied by a decreased ß-hCG level. Interestingly, co-treatment with the PPARγ antagonist GW9662 reversed the TBBPA-mediated changes in PPARγ protein expression but, according to ß-hCG secretion, potentiated an inhibitory effect of TBBPA. Additionally, in our study, we assessed the ability of TBBPA to increase progesterone levels in JEG-3 cells compared with those of controls. Finally, in the present study, we demonstrated that TBBPA at all of the tested doses significantly increased caspase-3 activity compared with that of the vehicle control. The apoptotic action of TBBPA was also confirmed by Hoechst 33342 staining. These results showed the up-regulation of PPARγ protein expression after TBBPA exposure in human placental cells. Although co-treatment with antagonist of PPARγ reversed the TBBPA-mediated increase in this protein expression and restored it to the control level, it did not reverse the effect on ß-hCG secretion. This indicated that the mechanism of TBBPA-induced changes in ß-hCG secretion is PPARγ-independent.

Síndrome del coriocarcinoma / Choriocarcinoma syndrome

OBJETIVO: Conocer la posibilidad de desarrollo de síndrome de coriocarcinoma como una complicación potencialmente mortal en pacientes con dicha patología. MÉTODO: El Síndrome del Coriocarcinoma consiste en manifestaciones hemorrágicas de las metástasis en el cáncer avanzado de células germinales que contienen elementos de gran volumen de coriocarcinoma. Debe sospecharse en pacientes con alta masa tumoral, metástasis múltiples y marcadores tumorales elevados propios de los tumores de células germinales. Suelen aparecer antes y durante el inicio del tratamiento sistémico con quimioterapia. La falta de diagnóstico puede conllevar consecuencias fatales y pueden requerir medidas agresivas de diagnóstico y terapéuticas como la cirugía. Además debe prevenirse realizando una buena estrategia terapéutica que incluya un equipo interdisciplinar, pudiéndose plantear diferir la cirugía testicular e iniciar previamente el tratamiento con quimioterapia. RESULTADO: Presentamos dos casos de dos hombres con el diagnóstico síndrome de coriocarcinoma sobre metástasis hepáticas. Aportamos imágenes ecográfica y por TAC de los dos casos de hemorragia sobre las metástasis hepáticas y las características radiológicas peculiares de ambos casos, nunca antes publicadas. CONCLUSIONES: Debe existir un alto índice de sospecha de complicaciones potencialmente mortales en pacientes que presentan tumores de células germinales con componente de coriocarcinoma, entre ellas el desarrollo del Síndrome de Coriocarcinoma potencialmente mortal

OBJECTIVE: To explore the possibility of choriocarcinoma syndrome developing as a potentially fatal complication in patients with this pathology. METHOD: Choriocarcinoma syndrome consists of hemorrhagic manifestations of metastases in advanced germ cell cancer containing large elements of choriocarcinoma. It should be suspected in patients with high tumor mass, multiple metastases and elevated tumor markers characteristic of germ cell tumors. It usually occurs before and during the onset of systemic treatment with chemotherapy. Failure to diagnose it can lead to fatal consequences and may require aggressive diagnostic and therapeutic measures such as surgery. It can also be prevented by developing a good therapeutic strategy that includes an interdisciplinary team, raising the possibility of deferring testicular surgery and beginning chemotherapy beforehand. RESULTS: We report two cases of men with the diagnosis of choriocarcinoma syndrome on liver metastases. We provide ultrasound and CT images of the two cases of hemorrhage on liver metastases and radiological characteristics peculiar to each case that have never been published before. CONCLUSIONS: There should be a high index of suspicion of life-threatening complications in patients with germ cell tumors with a choriocarcinoma component, including the development of life-threatening choriocarcinoma syndrome

Choriocarcinoma in northwestern Nigeria: a histopathological review.

AIMS AND OBJECTIVES: Gestational choriocarcinoma is a malignant form of gestational trophoblastic disease with a highly aggressive biologic behavior and responds well to chemotherapy. The objective of this study is to analyse the various histological features of this neoplasm as seen in Ahmadu Bello University Teaching hospital, ( ABUTH ) Zaria, determine its incidence, and compare with other studies. MATERIALS AND METHODS: The bench registers were used to retrieve the request forms, slides, and tissue blocks. The slides were all stained with standard haematoxylin and Eosin. The histological criteria published by Gehrig and van Lee was used to diagnose the tumours and grading of the cases from grade I to III. RESULTS: Forty three cases were studied and these formed 4.9% of all products of conception and 37.7% of all gestational trophoblastic diseases. The peak age of incidence was in the third and fourth decades of life with vaginal bleeding as the leading mode of presentation. Extensive histopathological analysis and grading revealed haemorrhage, necrosis diamorphic appearance and pleomorphism as the most frequent features. CONCLUSION: Gestational choriocarcinoma is a common problem in Zaria, North- Western Nigeria with an incidence of 1 in 1039 deliveries. Haemorrhage, necrosis, diamorphic appearance and pleomorphism were the most frequent histological features. Health education and early detection are of paramount importance in reducing morbidity and mortality.

Forskolin-induced differentiation of BeWo cells stimulates increased tumor growth in the chorioallantoic membrane (CAM) of the turkey (Meleagris gallopavo) egg.

Invasiveness of BeWo cells has been assessed in a variety of assay systems including matrigel and mouse. At the same time BeWo cells are mostly used as model system for trophoblast fusion. Here we aimed to test the properties of BeWo cells in a combined approach. We forced BeWo cells to differentiate by culturing the cells in the presence of forskolin and then used these cells for invasion assays on the chorioallantoic membrane (CAM) of the turkey. The chorioallantoic membranes of turkey eggs were incubated with medium containing forskolin, BeWo cells cultured in medium alone, BeWo cells cultured in forskolin and washed, and BeWo cells cultured in forskolin and used directly for application. Suspensions were applied onto ten CAM per condition. For local tumor formation eggs were checked for tumor development every 24h macroscopically for up to 12 days and immunohistochemistry for cytokeratin 18 and Ki-67 were used for further analysis. Forskolin alone did not have any deleterious effect on the CAM. When the CAM was incubated with BeWo cells cultured in medium 40% of the eggs developed a macroscopically visible tumor. BeWo cells stimulated with forskolin and washed induced tumor growth in 50% of the eggs, while forskolin stimulated BeWo cells applied directly onto the CAM induced tumor growth in 70% of the eggs. Forced differentiation of BeWo cells by forskolin may lead to syncytial fusion in a plastic culture dish. Under the conditions used here, i.e. in direct contact to a living tissue, forskolin-induced differentiation of BeWo cells leads to an increase in tumor formation in the CAM. Thus BeWo cells may use signaling pathways to decide for both differentiation pathways similar to primary trophoblast depending on the environment.

Morphological and electrical properties of human trophoblast choriocarcinoma, BeWo cells.

The syncytiotrophoblast of the human placenta arises from fusion of stem cells called cytotrophoblasts. The molecular mechanisms associated with cell fusion and syncytiation of cytotrophoblastic cells remain largely unknown. In the present study, we investigated the morphological and electrical properties of BeWo cells, a human choriocarcinoma-derived trophoblast cell model, with several features of the human cytotrophoblast. Cultured cells tended to cluster, but only fused into small, multinucleated syncytia in the presence of cAMP (72 h). The morphological features of both the actin and microtubular cytoskeletons indicated that within 72 h of constant exposure to cAMP, intracellular cortical actin cytoskeleton disappeared, which was the most prominent inducing factor of multi-nucleation. The presence of the cation channel protein, polycystin-2 (PC2), a TRP-type cation channel, associated with placental ion transport in term human syncytiotrophoblast, co-localised with acetylated tubulin in midbodies, but was found non-functional under any conditions. Different electrical phenotypes were observed among control BeWo cells, where only 26% (8 of 31 cells) displayed a voltage-dependent outwardly rectifying conductance. Most quiescent BeWo cells had, however, a low, slightly outwardly rectifying basal whole cell conductance. Acute exposure to intracellular cAMP (<15 min) increased the whole cell conductance by 122%, from 0.72 nS/cell to 1.60 nS/cell, and eliminated the voltage-regulated conductance. The encompassed evidence indicates that the early events in BeWo cell fusion and syncytiation occur by cAMP-associated changes in ionic conductance but not morphological changes associated to chronic exposure to the second messenger. This suggests a tight regulation, and important contribution of cation conductances in cytotrophoblastic cells prior to syncytiation.

Hypoxic upregulation of glucose transporters in BeWo choriocarcinoma cells is mediated by hypoxia-inducible factor-1.

Placental hypoxia has been implicated in pregnancy pathologies, including fetal growth restriction and preeclampsia; however, the mechanism by which the trophoblast cell responds to hypoxia has not been adequately explored. Glucose transport, a process crucial to fetoplacental growth, is upregulated by hypoxia in a number of cell types. We investigated the effects of hypoxia on the regulation of trophoblast glucose transporter (GLUT) expression and activity in BeWo choriocarcinoma cells, a trophoblast cell model, and human placental villous tissue explants. GLUT1 expression in BeWo cells was upregulated by the hypoxia-inducing chemical agents desferroxamine and cobalt chloride. Reductions in oxygen tension resulted in dose-dependent increases in GLUT1 and GLUT3 expression. Exposure of cells to hypoxic conditions also resulted in an increase in transepithelial glucose transport. A role for hypoxia-inducible factor (HIF)-1 was suggested by the increase in HIF-1alpha as a result of hypoxia and by the increase in GLUT1 expression following treatment of BeWo with MG-132, a proteasomal inhibitor that increases HIF-1 levels. The function of HIF-1 was confirmed in experiments where the hypoxic upregulation of GLUT1 and GLUT3 was inhibited by antisense HIF-1alpha. In contrast to BeWo cells, hypoxia produced minimal increases in GLUT1 expression in explants; however, treatment with MG-132 did upregulate syncytial basal membrane GLUT1. Our results show that GLUTs are upregulated by hypoxia via a HIF-1-mediated pathway in trophoblast cells and suggest that the GLUT response to hypoxia in vivo will be determined not only by low oxygen tension but also by other factors that modulate HIF-1 levels.

Estrogen-like response to p-nonylphenol in human first trimester placenta and BeWo choriocarcinoma cells.

p-Nonylphenol (p-NP) is a metabolite of alkylphenol ethoxylates used as surfactants in the manufacturing industry. Although it is reported to have estrogenic activity and to be transferred from the mother to the embryo, no data are available on its effects on the development of the human placenta. In the present study, we investigated estrogen receptors' (ERs) expression in the first trimester human placenta. Using an in vitro model of chorionic villous explants, we then compared the effects of p-NP and 17beta-estradiol (17beta-E2). Finally, a trophoblast-derived choriocarcinoma cell line, BeWo, was used as a model of trophoblast cell differentiation. Our results showed that the first trimester placenta expresses three ER-alpha isoforms of 67, 46, and 39 kDa and one ER-beta isoform of 55 kDa. Immunohistochemistry revealed the expression of ER-alpha in the villous cytotrophoblast, whereas ER-beta was mainly expressed by the syncytiotrophoblast. Treatment of explant cultures with p-NP (10(-9)M) and 17beta-E2 (10(-9)M) significantly increased beta-hCG secretion and cell apoptosis but did not modify ER expression. After 72 h of exposure, hormone release was significantly higher in p-NP- than 17beta-E2-treated explant cultures. By this time, cleavage of caspase-3 was evident in cultures treated with 17beta-E2 and p-NP. In BeWo cells, a caspase-3 band of 20-16 kDa was evident after 1 h of treatment with p-NP and after 24 h of treatment with 17beta-E2 or forskolin. These findings suggest that the human trophoblast may be highly responsive to p-NP and raise concern about maternal exposure in early gestation.

Induction of endogenous Nrf2/small maf heterodimers by arsenic-mediated stress in placental choriocarcinoma cells.

Exposure to inorganic arsenic has been associated with various forms of cancer, nervous system pathogenesis, and vascular diseases, as well as reproductive and developmental toxicity. Here, the effect of inorganic arsenic on placental JAR choriocarcinoma cells was assessed. The nuclear protein levels of the CNC transcription factor Nrf2 were strongly induced in the presence of arsenic. Dosage response experiments showed that 0.5 microM of arsenic is sufficient to augment Nrf2 levels. The expression of the Nrf2 dimerization partners MafG and MafK appeared not to be modulated by arsenic, whereas MafF protein levels were slightly increased. Arsenic also induced the binding of endogenous Nrf2/small Maf DNA-binding complexes to a stress response element (StRE) recognition site. In addition, arsenic caused oxidative stress in the choriocarcinoma cell model as evidenced by an increase in intracellular H2O2 levels. Expression of the enzyme heme oxygenase-1 (HO-1), a known Nrf2 target gene, was upregulated by exposure of JAR cells to arsenic. These results suggest that Nrf2/small Maf heterodimers may play an important role in the response to arsenic-mediated stress in placental cells.

Inhibition of DLX4 promotes apoptosis in choriocarcinoma cell lines.

Homeodomain (HDM) proteins encoded by homeobox (HBX) genes represent a large family of transcriptional factors that control differentiation and development in certain cell types. DLX4 is a member of Distal-less (DLX) family of HBX genes. Recent studies have demonstrated that abnormal expression of DLX4 is present in several types of human tumors, such as breast cancer, leukemia and colon cancer. In the present study, we investigated DLX4 mRNA and protein expression in both normal placental tissues and human choriocarcinoma cell lines. Also, using RNA interference (RNAi) technique, we knocked down the expression of DLX4 and examined apoptosis in JEG-3 cells. Our studies demonstrated that DLX4 RNAi inhibited DLX4 mRNA expression and decreased DLX4 protein mass specifically and effectively, potentially enhancing apoptosis. Moreover, we examined expression of caspase-3 and caspase-8, and found that both caspases were increased after DLX4 knockdown. However, DLX4 RNAi did not influence Bax expression in JEG-3 cells. In conclusion, this study suggests that DLX4 may be involved in the survival of human choriocarcinoma cells, which may be mediated by the inhibition of apoptosis. The detailed mechanism needs further investigation.

Gestational trophoblastic disease: pictorial review.

Ultrasound is the modality of choice for evaluating normal or abnormal first trimester pregnancy. Sonography can usually provide a specific diagnosis in abnormal first trimester bleeding. When the sonographic appearance is correlated with the clinical presentation, accurate diagnosis is possible in most cases of gestational trophoblastic disease (GTD). Partial or complete hydatidiform moles can be diagnosed in early gestation. However certain cases will be missed if the curettage material is not sent for pathologic examination. Sometimes molar pregnancies have very unusual sonographic appearances. Sonography and Doppler imaging are helpful in diagnosing gestational trophoblastic disease, in determining whether invasive disease is present, in detecting recurrent disease, and in following the effectiveness of chemotherapy. This pictorial essay describes the pathogenesis, epidemiology, and sonographic spectrum of gestational trophoblastic disease.

Hemorragia digestiva e invaginación intestinal por coriocarcinoma intestinal / Gastrointestinal bleeding and intestinal invagination due to intestinal choriocarcinoma

No disponible

Expression of the 5-HT2A serotoninergic receptor in human placenta and choriocarcinoma cells: mitogenic implications of serotonin.

Serotonin (5-hydroxytryptamine, 5-HT) has diverse physiological functions and acts as a mitogen in a variety of cell types, including bovine placental cells. It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor types. Previous studies have reported the presence of 5-HT(2) binding sites in human placental trophoblastic cells, but this has never been confirmed at the molecular level. In this study, we demonstrated that the 5-HT(2A) receptor subtype is fully expressed in the human choriocarcinoma cell lines JEG-3 and BeWo as well as in normal human placental tissue. DNA sequencing has confirmed that the 5-HT(2A) receptor present in these cell lines and tissues is identical to the human 5-HT(2A) receptor found in platelets and in the cerebral cortex. This receptor was localized by immunofluorescence on the plasma membrane, in JEG-3 and BeWo cells. Furthermore, MTT proliferation assays revealed a positive effect of 5-HT on the proliferation of JEG-3 and BeWo cells. These results suggest that 5-HT constitutes a potent mitogen for neoplastic placental cells.

Expression, regulation, and function of paired-box gene 8 in the human placenta and placental cancer cell lines.

Pax proteins are transcriptional regulators that control a variety of developmental decisions in vertebrates. During development, the paired-box gene 8 (PAX8) is expressed in the thyroid, kidney, and several areas of the central nervous system. It is also expressed in the adult thyroid gland, in which it mediates TSH-induced modulation of the expression of important genes, such as those encoding thyroglobulin, thyroperoxidase, and the sodium/iodide symporter (NIS). Thus far, placental expression of PAX8 has been described only in mice. In the present study, we show that PAX8 is also expressed in the human placenta at term. In an in vitro model of placental cancer, the JAR choriocarcinoma cell line, human chorionic gonadotropin (hCG) increased levels of PAX8 mRNA and protein, and gel retardation assays indicated that the up-regulation of PAX8 protein expression is associated with an increase in its DNA-binding activity. The effects of hCG were mimicked by forskolin, indicating that they are cAMP dependent. Levels of mRNA for the Wilms' tumor 1 (WT1) and NIS genes were increased in JAR cells by hCG treatment, whereas overexpression of PAX8 increased only levels of WT1 mRNA. In cells transfected with PAX8-specific small interfering RNA, the stimulatory effects of hCG on WT1 mRNA levels were abolished, but hormonal enhancement of NIS mRNA levels was unchanged. These findings indicate that, in JAR cells, hCG activates a cAMP-dependent pathway that can up-regulate WT1 expression through PAX8.

Modulation of ezrin and E-cadherin expression by IL-1beta and TGF-beta1 in human trophoblasts.

OBJECTIVES: The present study examines the effects of IL-1beta and TGF-beta1 in modulation of ezrin, E-cadherin, CD44 and beta-catenin expression in human trophoblast cells which may lead to their altered cytoskeleton dynamics during cell-to-cell and cell-to-matrix interactions. METHODS: Trophoblast (extravillous and villous) cells isolated and purified from early and term placentae and human choriocarcinoma cell line JEG-3 used in this study were challenged with either IL-1beta or TGF-beta1 (10 ng/ml) for 12 h following which RT-PCR was performed for ezrin, E-cadherin, CD44 and beta-catenin. Immunolocalization of these proteins was carried out in the chorionic villi as well as in the cultured cells stimulated by the cytokines. Western Blot was also performed to study the regulation of ezrin and E-cadherin in primary extravillous, villous and term trophoblast by these cytokines. Scanning electron microscopy (SEM) and Matrigel Invasion Assay was used to study the effect of these cytokines on cellular morphology and invasion. RESULTS: IL-1beta induced a down regulation in the expression of ezrin, E-cadherin and beta-catenin while upregulation of CD44 message in both primary trophoblast and JEG-3 cells. On the contrary, TGF-beta1 exhibited just an opposite effect, i.e. up regulation of ezrin, E-cadherin, beta-catenin, and down regulation of CD44. These observations were further corroborated with the immunolocalization findings of the above proteins in first trimester and term villous tissue, the former having predominance of IL-1beta and the latter of TGF-beta1 [Am. J. Reprod. Immunol. 48 (2002) 210]. Cellular morphology as observed through SEM revealed an enhanced cell-to-matrix adhesion with poor cell-cell interaction following IL-1beta challenge and a strong intercellular adhesion with weak cell-to-matrix interaction in presence of TGF-beta1. Crystal violet staining and Matrigel invasion revealed a higher invasion index following IL-1beta challenge and a low invasion index following TGF-beta1 challenge. CONCLUSION: IL-1beta mediated increased cell-to-matrix interaction with reduced cell-to-cell adhesion along with reduced ezrin and E-cadherin expression is associated with enhanced invasiveness while TGF-beta1 mediated up regulation of cell-to-cell adhesion with reduced cell-to-matrix interaction along with an increased ezrin and E-cadherin expression, is associated with reduced invasiveness, along with an altered cellular morphology. These facts therefore indicate the possible role of the two cytokines during cell motility and invasion through alteration of cell-matrix and cell-cell interaction.

Analysis of a candidate gene associated with growth suppression of choriocarcinoma and differentiation of trophoblasts.

OBJECTIVE: To isolate a choriocarcinoma suppressor gene and analyze its structure and function. STUDY DESIGN: We constructed a polymerase chain reaction-based subtracted fragmentary cDNA library between normal placental villi and choriocarcinoma cell line CC1. A novel homeobox gene, designated NECC1 (not expressed in differ choriocarcinoma clone 1), is included in this library. We analyzed the structure and function of NECC1 with molecular biology. RESULTS: NECC1 comprises an open reading frame of 219 nucleotides encoding 73 amino acids and contains a homeodomain as a consensus motif. NECC1 is located on human chromosome 4q11-q12, and its expression is ubiquitous in the brain, placenta, lung, smooth muscle, uterus, bladder, kidney and spleen. Normal placental villi abundantly expressed NECC1, but all choriocarcinoma cell lines examined and most surgically removed choriocarcinoma tissue samples failed to express it. We transfected this gene into choriocarcinoma cell lines and observed remarkable alterations in cell morphology and suppression of in vivo tumorigenesis. Induction of chorionic somatomammotropin hormone 1 by NECC1 transfection suggested differentiation of choriocarcinoma cells to syncytiotrophoblast-like cells. CONCLUSION: Our results suggest that loss of NECC1 expression is involved in malignant conversion of placental trophoblasts.

Molecular biology of gestational trophoblastic neoplasia: a review.

Gestational trophoblastic diseases are interrelated conditions characterized by abnormal growth of chorionic tissues with varying propensitiesfor local invasion and metastases. These diseases are characterized by altered expression of several growth regulatory factors and oncogenes. On the basis of the expression of various oncogenes and growth factors, partial mole appears to be more like normal placenta, while complete mole seems to be more like choriocarcinoma. These results may have both prognostic and therapeutic consequences and provide insight into the relationship between normal placenta and gestational trophoblastic diseases.

Potential regulation of PTH/PTHrP receptor expression in choriocarcinoma cells.

OBJECTIVE: Parathyroid hormone-related peptide (PTHrP) have been found to be expressed in a variety of human tumors. Parathyroid hormone-related peptide is known as the major mediator of humoral hypercalcemia of malignancy, may also regulate placental calcium flux, uterine contraction and fetal tissue development. The purpose of this study is to evaluate the expression of PTH/PTHrP receptor in choriocarcinoma JAR cell line. METHODS: This study was carried out at the Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia, between November 2002 and August 2003. Choriocarcinoma JAR cell line treated for 12 and 72 hours with epidermal growth factor, (EGF) (20ng/ml), estradiol, E2 (10(-8) M), dexamethasone, (DEX) (10(-8) M) or 1,25 dihydroxycholecalciferol, 1,25 (DHCC) (10(-8) M). We investigated the expression of parathyroid hormone (PTH)/PTHrP receptor in JAR cell line with these treatments compared with untreated JAR cells. The PTH/PTHrP receptor expression were detected with 3.3nM 125I-PTHrP-34Tyrosine. RESULTS: The expression of the receptors at 12 hours were increased following exposure to EGF, E2 or DEX, whereas 1,25 DHCC inhibited the receptor expression. In further experiments at 72 hours with the same treatments, the receptors expression were remarkably increased with EGF, E2 or DEX, whereas, 1,25 DHCC inhibited the receptor expression in these cells. CONCLUSION: These data suggested that in JAR cells, The EGF, E2 and DEX upregulated the PTH/PTHrP receptor expression, whereas the 1,25 DHCC down-regulated the PTH/PTHrP receptor, and the 1,25 DHCC may play an important role as antiproliferative drug for choriocarcinoma.

Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid.

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that has structural similarity to TSH. At the time of the peak hCG levels in normal pregnancy, serum TSH levels fall and bear a mirror image to the hCG peak. This reduction in TSH suggests that hCG causes an increased secretion of T4 and T3. Women with hyperemisis gravidarum often have high hCG levels that cause transient hyperthyroidsm. In the vast majority of such patients, there will be spontaneous remission of the increased thyroid function when the vomiting stops in several weeks. When there are clinical features of hyperthyroidism, it is be reasonable to treat with antithyroid drugs or a beta-adrenergic blocker, but treatment is rarely required beyond 22 weeks of gestation. Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors, either hydatiditform mole or choriocarcinoma. The diagnosis of hydatidiform mole is made by ultrasonography that shows a 'snowstorm' appearance without a fetus. Hydatidiform moles secrete large amounts of hCG proportional to the mass of the tumor. The development of hyperthyroidism requires hCG levels of >200 U/ml that are sustained for several weeks. Removal of the mole cures the hyperthyroidism. There have been many case reports of hyperthyroidism in women with choriocarcinoma and high hCG levels. The principal therapy is chemotherapy, usually given at a specialized center. With effective chemotherapy, long-term survival exceeds 95%. A unique family with recurrent gestational hyperthyroidism associated with hyperemesis gravidarum was found to have a mutation in the extracellular domain of the TSH receptor that made it responsive to normal levels of hCG.