Identification of differentially expressed genes in pathways of cerebral neurotransmission of anovulatory mice.

Polycystic ovary syndrome is the classic example of loss of functional cyclicity and anomalous feedback. In this case, the excessive extra-glandular production and conversion of androgens to estrogens are the pathophysiological basis of the chronic anovulation. The literature describes an experimental model of the polymicrocystic ovary in obese diabetic mice with insulin resistance. The fact that these animals exhibit obesity, insulin resistance, and infertility demonstrates their skill as an experimental model for polycystic ovary. A recent study using long protocol for up to 40 weeks showed that anovulatory and obese mice transplanted with adipose tissue from animals with normal weight have multiple changes in their phenotype. These changes include reduction of body weight, prevention of obesity, insulin level normalization, and insulin tolerance tests, preventing the elevation of steroids and especially the reversal of fertility restoration with anovulation. Considering that there are close relationships between the ovulation process and the central nervous system, we propose to evaluate the gene expression levels of 84 different genes involved in neurotransmission and insulin pathways in addition to examining the neurolipidosis differential murine brain before and after reversal of anovulation. The present study showed changes in gene expression of molecular markers in brain tissue of animals for brain neurotransmission pathways as well as pathways for insulin. GABAergic genes, muscarinic, serotonin receptors, receptor tyrosine kinase, and genes of interleukin 6 showed overexpression profile. There was also a change in the lipid content in anovulatory brain, obesity, and insulin resistant mice (Ob-/Ob-) compared with controls. The re-introduction of leptin in these animals appears to reverse, at least in part, this profile.

Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer.

The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.

Application of fluorescence in situ hybridization (FISH) as a tool to aid cytogenetics in 1,409 fetal samples.

AIM: To evaluate the technical application of fluorescence in situ hybridization (FISH) as a support to classical cytogenetic in numerical chromosomal aneuploidies studies in samples of amniotic fluid, chorionic villus, and fetal loss. MATERIALS AND METHODS: The authois performed cytogenetic analyses in 1,409 patients (678 amniocentesis, 512 chorionic villus samples, and 219 spontaneous abortions) during one year. FISH molecular study aided traditional cytogenetic in 90 cases. These cases were indicated based on the diagnostic hypothesis of each patient or when no cellular growth was obtained. The authors standardized the FISH in discoloured slides. RESULTS: They had 85% positive FISH in amniotic fluid, 70% in chorionic villus, and 90% in abortion material using 13, 18, 21 X and Y centromeric probes. It showed 12% of altered FISH in amniotic fluid (100% trisomies), 10% in chorionic'villus (50% trisomy and 50% X - monosomy), and 22% in abortion material (50% trisomy, 25% X-monosomy, and 25% triploidy). FISH and cytogenetic analysis confirmed the results. CONCLUSION: This technique revolutionized clinical and research applications of cytogenetics. In this particular paper, FISH was a valuable and reliable technique to promptly identify rapid detection of aneuploidies in interphase cells, metaphase spread and paraffin-embedded samples. It is hoped that, in the future, the economic viability of array CGH and FISH, with the decreasing cost of testing and their genomics advantages can be incorporated as routine and customized in the approach of prenatal diagnosis.

Polymorphisms in CYP17, COMT, and ESR1 genes in women after menopause and association with bone mineral density.

In this study, we evaluated genetic factors related to the mineral density during post-menopause. We evaluated 110 women in the first 5 years post-menopause, without previous hormone replacement therapy. Cytochrome P450 17 (CYP17) (rs743572), catechol-O-methyl transferase (COMT) (rs4680), and estrogen receptor 1 (ESR1) (rs9322331) were examined for the presence of polymorphisms. Clinical data were collected by anamnesis; all patients had the osseous densitometry examined using a lunar instrument to determine mineral osseous densitometry in the lumbar column (L2-L4). CYP17, COMT, and ESR1 genotyping was carried out by polymerase chain reaction with DNA collected from buccal swabs. The average age was 51.96 years. The average weights of the patients in control and osteopenia groups were 70.25 ± 12.00 and 62.45 ± 11.64, respectively (P = 0.001) and body mass index (P = 0.006; control: 29.43 ± 5.25; osteopenia: 26.72 ± 4.57). Related to CYP17 polymorphisms, 28.18% of women were TT (wild-type homozygous), 60% were TC (heterozygous), and 11.82% were CC (mutated homozygous). Related to COMT polymorphisms, 53.64% of women were GG (wild-type homozygous), 37.27% were GA (heterozygous), and 9.09% were AA (mutated homozygous). Related to ESR1, 53.64% of women were CC (wild-type homozygous), 40.91% were CT (heterozygous), and 5.45% were TT (mutated homozygous). The ESR1 variant allele was significantly higher in the osteopenia group when compared with women in the normal group (P = 0.02). ESR1 may be associated with low mineral osseous densitometry, while CYP17 and COMT gene polymorphisms were not associated with mineral osseous densitometry.

Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1--CYP1A1 and catechol-O-methyl transferase--COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or absence of cervical cancer. Genotypes of 222 women were analyzed: a) 81 with cancer of the cervix treated at the Cancer Hospital Alfredo Abram, between June 2012 and May 2013, with diagnosis confirmed surgically and/or through histomorphological examination; and b) 141 healthy women who assisted at the Endocrine Gynecology and Climacteric Ambulatory, Department of Gynecology, UNIFESP-EPM. These polymorphisms were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis and visualized on 3% agarose gels stained with ethidium bromide. We found a significant association between the frequency of the CYP1A1 polymorphism and the development of cervical cancer. A statistical difference was observed between patient and control groups for CYP1A1 polymorphism genotype distributions (P < 0.05). However, no significant differences were found in the COMT gene polymorphism genotype distributions between the patient and control groups (P > 0.05) or between other risk variables analyzed. The CYP1A1 gene involved in the metabolic pathway of sex steroids might influence the emergence of pathological conditions such as cervical cancer in women who carry a mutated allele, and result in 1.80 and 13.46 times increased risk for women with heterozygous or homozygous mutated genotypes, respectively.

p27kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis.

We hypothesized that p27(kip1) overexpression can regulate endometriosis cell proliferation, apoptosis and vascular endothelial growth factor (VEGF) expression in the endometrium. The overexpression of p27(kip1) was obtained by transduction of p27(kip1) in primary cultures of endometrium obtained from women with endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27(kip1) expression in endometrial cells primary culture. The effect of p27(kip1) overexpression was elucidated through the cell proliferation evaluation and the expression of the cell cycle-related proteins p16, p21, p27, and p53. Cell cycle and apoptosis in endometrial cells from women with and without endometriosis were also evaluated. The VEGF levels were evaluated 1 and 7 days after transduction. The experiments were performed using Immunofluorescence stainings and flow cytometry technique. The cell proliferation statistically diminished markedly following p27(kip1) overexpression in the endometriosis group. This process was accompanied, however, by a statistically significant modulation of the cell cycle-related proteins p16, p21, p27 and p53 markedly increase following p27(kip1) overexpression in the endometriosis group (p < 0.001) and an increase in apoptotic cells was observed. In the endometriosis group, significant downregulation of VEGF expression was observed 7 days after p27(kip1) overexpression, attaining levels strikingly similar to those observed in the control endometrial cells. The findings of this study showed a link between the cell cycle control protein (p27(kip1)) and angiogenesis (VEGF). Our results, also reinforces the background of endometrial dysfunction as part of the origin of endometriosis. We believe that better knowledge of endometrium milieu and the establishment of the link between different, previously describe, altered pathways in this tissue can facilitate future genetic cell therapy.

TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population.

We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53 11 Glu/Gln or Lys (GAG->CAG or AAG), TP53 72 Arg/Pro (CCG->CCC), and TP53 248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53 11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. The genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/Lys); the homozygous variant genotype was not identified (P = 0.02). TP53 72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). The genotypic distribution in the endometriosis group was 16.15% homozygous wild-type (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53 248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53 72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis.

Persistence or clearance of human papillomavirus infections in women in Ouro Preto, Brazil.

Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for development of precursor lesions and cervical cancer. We investigate persistence and clearance of HPV infections and cofactors in unvaccinated women. Cervical samples of 569 women (18-75 years), received for routine evaluation in the Health Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 or GP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or persistence did not differ between groups infected by HPVs 18, 53, and 67. In low-risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV 11, 61, 72, or 81 infected samples were persistent in the follow-up. No statistically significant association was detected between persistent HPV infections and sociodemographic and behavioral characteristics analyzed. To study persistence or clearance in HPV infection allows the identification of risk groups, cofactors, and strategies for prevention of cervical cancer.

The relationship between estrogen receptor gene polymorphism and mammographic density in postmenopausal women.

OBJECTIVE: To assess the relationship between the presence of PVUII and XBAI polymorphisms in the estrogen receptor α gene and mammographic density in postmenopausal women. METHODS: For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinical or mammographic features were selected. Based on the ACR-BIRADS(®) 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized). Blood samples were available to extract DNA according to KIT GFX(®) protocol. PCR-RFLP was then used to identify the polymorphisms. RESULTS: There was a high degree of agreement among the three readers to determine the mammographic density (κ > 0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasts. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI polymorphism was found in 135 (71.4%) women. Parity (p = 0.02) and body mass index (p < 0.0001) were associated with mammographic density. It was observed that, for the XBAI polymorphism, women with two mutated alleles were approximately 2.5 times more likely to be classified in the dense breasts group (p = 0.003) and the presence of both wild alleles was associated with fibroglandular tissue replacement by fat (p = 0.02). CONCLUSIONS: There was no significant association of the PVUII polymorphism in the estrogen receptor α gene with mammographic density (p = 0.34). However, the XBAI polymorphism was observed at a higher mutated homozygous frequency in women with dense breasts and there was an increased frequency of wild-type homozygous and heterozygous women with fat-replaced breasts (p = 0.01).

Human papillomavirus infection in Brazilian women with normal cervical cytology.

We examined the prevalence of human papillomavirus (HPV) infection in a sample of Brazilian women presenting normal cervical cytology. Possible interactions between patient characteristics and HPV infection were analyzed in order to provide background data to improve cervical cancer screening and prophylaxis. Cervical samples of 399 women, received for routine evaluation in the Health Department of Ouro Preto, MG, Brazil, were subjected to HPV-DNA testing by PCR with MY09/11 primers. HPV-positive specimens were typed by RFLP. A structured epidemiological questionnaire was administered to each woman. HPV prevalence among these cytologically normal women was 11%. Twelve viral types were detected, the most common being HPV-16, -6, -61, -83, and -66. HPV was more prevalent in younger women; high-risk viral types were detected in 61% of the infected women and 27% of the infected women had multiple HPV infections. Significant associations of HPV infection were found with age, literacy, residence, marital status, lifetime number of sexual partners, and parity. We detected a great diversity of HPV types in women with normal cytology. This kind of information about local populations is useful for HPV prevention and vaccination strategies.

Influence of the CYP17 polymorphism on vasomotor symptoms in postmenopausal women: a pilot study.

OBJECTIVE: To evaluate the influence of CYP17 polymorphism on menopausal symptoms after estrogen treatment. METHODS: A total of 130 women were recruited, but only 100 of these were selected according to inclusion and exclusion criteria; they were treated with 0.3 mg/day conjugated equine estrogens. One year later, the study was completed by 71 women. The analysis of the Kupperman menopausal index symptoms was made with information provided by the patients on daily diary cards. Blood samples were analyzed and the women were divided into two groups based on the CYP17, 5'-untranslated region: group A (wild-type homozygote and heterozygote) and group B (mutated homozygote). RESULTS: The values for the Kupperman menopausal index were similar in both groups at baseline. The symptoms in both groups decreased after 1 year of treatment when compared to those at baseline. The improvement rate was approximately 27.09% and 32.18%, in groups A and B, respectively. The levels of estrogen after treatment were higher in both groups in comparison with the baseline values. The testosterone level rose in group B with the 1-year treatment (0.48 + 0.16 ng/ml), reaching a higher level than the level in group A after treatment. The sex hormone binding globulin (SHBG) level showed a significant increase after the 1-year treatment in group B, surpassing both the baseline and the after-treatment values in group A (p < 0.01). CONCLUSION: Our data suggest that the CYP17 polymorphism did not influence the action of estrogen on menopause symptoms during the 1-year treatment. The extra production of estrogen and androgen may have been countered by the elevation of SHBG levels.

Cytokine and hormonal profile in serum samples of patients undergoing controlled ovarian stimulation: interleukin-1beta predicts ongoing pregnancy.

BACKGROUND: Changes in the endometrium are not regulated exclusively by ovarian hormones; the immune system has also been implicated in normal endometrial function, similar to processes taking place during inflammatory and reparative path. Many cytokines are crucially important for reproductive processes, and the role of cytokines in the female reproductive system function has been broadly investigated during controlled ovarian stimulation (COS) for IVF attempts. The aim of this study was to evaluate the levels of serum cytokines and hormones, and the clinical outcomes of women who underwent COS and ICSI procedures. METHODS: The study prospectively included 96 patients (aged 22-43 years, unexplained or male infertility, n = 61; female infertility factors, n = 35) who underwent ICSI cycles. Serum levels of interleukin (IL-8, IL-6, IL-1beta, IL-10, IL-12), tumour necrosis factor and leukaemia-inhibitory factor (LIF) and the hormones FSH, estradiol, progesterone, anti-Mullerian hormone and Inhibin-B were measured on the day of oocyte retrieval. RESULTS: The ongoing pregnancy rate was 25.3%. The presence of serum IL-1beta positively affected the implantation rate (P = 0.004) and increased the chance of becoming pregnant by 15 fold. Furthermore, the percentage of patients with detectable serum IL-1beta levels who conceived (62.5%) was higher than those who failed to conceive (37.5%; P = 0.019). The LIF was undetectable in all serum samples, and no other factors influenced the clinical outcomes of patients undergoing ICSI cycles. CONCLUSIONS: Our findings revealed that detectable serum levels of IL-1beta on the day of oocyte retrieval in patients undergoing COS and ICSI are predictive of successful implantation and ongoing pregnancy.

Fas/CD95 promoter polymorphism gene and its relationship with cervical carcinoma.

OBJECTIVE: Apoptosis is an important fail-safe control in human papillomavirus (HPV)-associated carcinogenesis. We tested the hypothesis that the A/G polymorphism at -670 of Fas promoter is associated with an increased risk for cervical cancer, using a matched case-control setting. METHODS: The material in this case-control study consisted of 91 patients with cervical carcinoma and 176 population-based control subjects, recruited between 2002 and 2004; all the ethnic Brazilian women had histologically confirmed cervical carcinoma. Control subjects were age-matched; healthy women who were selected following a negative cervical cytology and normal colposcopy. Fas genotyping was performed using a PCR-RFLP technique. RESULTS: No significant difference existed in the distribution of the Fas polymorphisms (wild, heterozygous, mutant) between the cases and controls. The heterozygous (OR: 4.85, 95% CI: 1.1-22.6) genotypes among the younger (< 48 yrs) cancer patients were almost 5-fold increased, as compared with the wild type. No such increase was observed among the patients older than 48 years. CONCLUSIONS: Our data suggest that 670A/G polymorphism in the promoter region of the death receptor Fas is associated with an increased risk of cervical cancer among Brazilian women under 48 years. The mechanisms would be the inhibition of apoptosis by Fas -670G allele-mediated down-regulation of Fas transcription.

Prognostic markers of low-grade squamous intraepithelial lesions: the role of topoisomerase IIalpha and active caspase-3.

PURPOSE: To study the relationship between topoisomerase IIalpha, active caspase-3 expressions and HPV DNA in uterine cervices with low-grade squamous intraepithelial lesions (LSIL). METHODS: Forty women with LSIL and 32 without cervical neoplasia diagnosed through cytologic and histopathologic examination were evaluated regarding topoisomerase IIalpha and active caspase-3 expressions and HPV DNA detection using PCR (GP5/GP6) in cervicovaginal smears. RESULTS: The mean percentage of cells immunomarked by topoisomerase in the group with LSIL was 11.62% while in the control it was 4.13% (p < 0.0001). In the presence of HPV DNA, topoisomerase expression was higher in the group with productive viral infection than in nonneoplastic tissue (p = 0.004). Caspase-3 expression was observed in 17 patients with LSIL (42.5%) and in five without cervical neoplasia (15.63%). CONCLUSION: The use of topoisomerase IIalpha and active caspase-3 in cervical biopsies may help to define the prognosis of HPV cervical infection.

Study of p53 codon 72 polymorphism in patients with breast cancer.

Breast cancer is a common disease in Western societies, with an incidence of 46.31/100,000 women/year in Brazil. The tumor suppressor gene TP53 is one of the most studied genes regarding the presence of mutations. Indeed, 50% of all tumors are known to exhibit changes in the TP53 nucleotide sequence due to carcinogenic processes. As to the presence of polymorphism, the TP53 gene is polymorphic at the nucleotide residue 347 (codon 72). In the current study, we examine if this polymorphism is associated with the clinicopathological parameters of breast cancer patients in a Brazilian population. One hundred and thirteen patients with breast cancer were included. The polymorphic region of the TP53 gene was PCR-amplified from genomic DNA obtained from buccal cells. Specific primers for the Pro and Arg allele were used. Correlations of polymorphism with age, staging, nuclear grade, lymph node status, estrogen receptor status and lymphatic and/or blood vessel invasion were evaluated. Statistical analysis was performed using the Fisher's exact test. The frequency of p53 Arg/Arg was 57% and of the heterozygous allele Arg/Pro it was 39%. There was no correlation between polymorphism and clinicopathological parameters. According to our results, the TP53 polymorphism, at the 347 residue, is not associated with any clinicopathological findings of patients with breast cancer.

Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development.

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The chi(2) test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

Interleukin-6 polymorphisms and the risk of cervical cancer.

Recent data implicate that cytokine gene polymorphisms are important in pathogenesis of various neoplastic and nonneoplastic human diseases, and it was recently suggested that polymorphisms in interleukin (IL)-6 might increase the risk of gynecological malignancies, including cervical carcinomas. The aim of this case-control study is to compare the IL-6 polymorphisms in cervical cancer patients and healthy controls and to assess whether any of these polymorphisms would increase the risk of developing cervical cancer. The material in this case-control study consists of 56 patients with cervical carcinoma and 253 population-based control subjects, all ethnic Brazilian women. Control subjects were cancer-free women, following a negative cervical cytology and colposcopy. IL-6 genotyping was performed using a polymerase chain reaction-based restriction fragment length polymorphism. Distribution of the GG, GC, and CC genotypes in cases and controls was significantly different (P= 0.033). Compared with the GG genotype as reference, the adjusted odds ratio for the combined GC and CC genotypes in cancer patients was 1.90 (95% confidence interval, 1.1-3.4). These data suggest that women carrying at least one C genotype in their IL-6 promoter region (-174G-->C) are at higher risk of developing cervical cancer.

Differential gene expression profile reveals overexpression of MAP3K8 in invasive endometrioid carcinoma.

Gene microarray technology is highly effective in screening for differential gene expression and has hence become a popular tool in the molecular investigation of cancer. In the present study, cDNA microarrays containing 2,000 different genes were used to analyze gene expression profiles in ten human postmenopausal endometrioid-paired carcinoma specimens versus corresponding adjacent normal tissue to identify differentially expressed genes. In our study several genes were found differentially expressed. One of them was the MAP3K8, a gene that has never been described to be overexpressed in this kind of malignancy. To validate the differential expression of this gene as well as the membrane array, we performed semiquantitative reverse transcription-PCR analysis. MAP3K8 was found overexpressed in 30% of the endometrial carcinoma samples. To the best of our knowledge this is the first report showing the MAP3K8 oncogene linked to human endometrial carcinoma suggesting that it may be another molecule involved in human endometrial cancer.

Differential gene expression assessed by cDNA microarray analysis in breast cancer tissue under tamoxifen treatment.

Our purpose was to identify tamoxifen (TAM) responsive genes after 30 days of TAM treatment in tumor tissues obtained from women with breast cancer using microarray expression analysis. In our study, we identified 12 candidates to be considered as tamoxifen-modulated genes. Among them, we selected two candidates the TEGT BI-1 (testis enhanced gene transcript Bax Inhibitor-1) and the CD63 gene in order to further confirm their differential expression under tamoxifen effects. We observed that both were down-regulated in tumor tissues of patients during TAM treatment. TEGT is able to inhibit the expression of Bax, which is known to promote apoptosis. On the other hand, CD63 encodes a cell membrane protein and it seems to be involved in mechanisms of platelet activation, cell adhesion and cell motility. We therefore hypothesize that TAM would be able to modulate tumor growth by down-regulating genes involved in mechanisms such as cell cycle control, tumor invasion and metastasis.