TMEM48 promotes cell proliferation and invasion in cervical cancer via activation of the Wnt/ß-catenin pathway.

Transmembrane proteins (TMEMs), spanning the entire width of lipid bilayers and anchored to them permanently, exist in diverse cell types to implement a series of essential physiological functions. Recently, TMEM48, a member of the TMEM family, has been demonstrated to be closely associated with tumorigenesis. However, little is known about the specific role of TMEM48 in cervical cancer (CC). This study aimed to investigate the biological functions of TMEM48 in CC. The CCK-8 assay was performed to detect CC cell proliferation. The wound healing and transwell assays were conducted to measure cell migration and invasion, respectively. The levels of TMEM48, ß-catenin, T cell factor 1(TCF1) and axis formation inhibitor 2 (AXIN2) were examined by the western blot analysis. Xenograft models were established for the tumorigenesis assay in vivo. The results showed that TMEM48 was overexpressed in CC tissues and cell lines. Knockdown of TMEM48 significantly inhibited CC cell proliferation, migration and invasion in vitro and suppressed CC cell growth in vivo. In addition, the investigation on the molecular mechanisms indicated that TMEM48 down-regulation remarkably decreased the protein levels of ß-catenin, TCF1 and AXIN2 in CC cells and TMEM48 exerted its promoting effect on CC progression via activation of the Wnt/ß-catenin pathway. Taken together, our study suggested TMEM48 as a promising therapeutic target for CC treatment.

CircAGFG1 sponges miR-203 to promote EMT and metastasis of non-small-cell lung cancer by upregulating ZNF281 expression.

The circRNA circAGFG1 is reported to be important in triple-negative breast cancer progression. However, the mechanism of circAGFG1 in non-small-cell lung cancer (NSCLC) remains unknown. In this study, expression of circAGFG1 was determined by real-time PCR in 20 pairs of NSCLC tissues and adjacent tissues. Next, functional experiments with circAGFG1 were performed in vitro to evaluate the role of circAGFG1 in tumor metastasis and growth. Meanwhile, a dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were used to explore the interaction between circAGFG1 and miR-203. Our results revealed that expression levels of circAGFG1 and miR-203 are upregulated in non-small-cell lung cancer tissues. CircAGFG1 enhances NSCLC cell proliferation, invasion, migration and epithelial-mesenchymal transition in vitro. Mechanistic analyses indicated that circAGFG1 acts as a sponge for miR-203 to repress the effect of miR-203 on its target, ZNF281. In conclusion, our study suggests that circAGFG1 promotes NSCLC growth and metastasis though a circAGFG1/miR-203/ZNF281 axis and may represent a novel therapeutic target.

HIV-1 infection increases microRNAs that inhibit Dicer1, HRB and HIV-EP2, thereby reducing viral replication.

HIV-1 is the causative agent of AIDS (Autoimmune Deficiency Syndrome). HIV-1 infection results in systemic CD4+ T cell depletion, thereby impairing cell-mediated immunity. MicroRNAs are short (~22 nucleotides long), endogenous single-stranded RNA molecules that regulate gene expression by binding to the 3' untranslated regions (3' UTR) of mRNA transcripts. The relation between HIV-1 infection and human miRNA expression profile has been previously investigated, and studies have shown that the virus can alter miRNA expression and vice versa. Here, we broaden the understanding of the HIV-1 infection process, and show that miRNA-186, 210 and 222 are up-regulated following HIV-1 infection of human Sup-T1 cells. As a result, the host miRNA target genes: Dicer1 (Double-Stranded RNA-Specific Endoribonuclease), HRB (HIV-1 Rev-binding protein) and HIV-EP2 (Human Immunodeficiency Virus Type I Enhancer Binding Protein 2), are down-regulated. Moreover, testing the miRNA-gene anti- correlation on the Jurkat and the HeLa-MAGI cell lines demonstrated the ability of the miRNAs to down-regulate viral expression as well. To conclude, we found that human miR-186, 210 and 222 directly regulate the human genes Dicer1, HRB and HIV-EP2, thus may be filling key roles during HIV-1 replication and miRNA biogenesis. This finding may contribute to the development of new therapeutic strategies.

Dhh1 is a member of the SESA network.

The correct separation of chromosomes during mitosis is necessary to prevent genetic instability and aneuploidy, which are responsible for cancer and other diseases, and it depends on proper centrosome duplication. In a recent study, we found that Smy2 can suppress the essential role of Mps2 in the insertion of yeast centrosome into the nuclear membrane by interacting with Eap1, Scp160, and Asc1 and designated this network as SESA (Smy2, Eap1, Scp160, Asc1). Detailed analysis showed that the SESA network is part of a mechanism which regulates translation of POM34 mRNA. Thus, SESA is a system that suppresses spindle pole body duplication defects by repressing the translation of POM34 mRNA. In this study, we performed a genome-wide screening in order to identify new members of the SESA network and confirmed Dhh1 as a putative member. Dhh1 is a cytoplasmic DEAD-box helicase known to regulate translation. Therefore, we hypothesized that Dhh1 is responsible for the highly selective inhibition of POM34 mRNA by SESA.

High-mobility group box 1 protein-mediated necroptosis contributes to dasatinib-induced cardiotoxicity.

Dasatinib shows remarkable activity against imatinib-refractory chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL). However, severe cardiovascular toxicity limits the clinical applications of dasatinib. Since the underlying mechanism of dasatinib-induced cardiotoxicity is still elusive, we aim to clarify this. Recent studies have shown that necroptosis and apoptosis participate in multiple toxicity development. Here, we first report that dasatinib could directly induce cardiomyocytes death, as analyzed by the Sulforhodamine B (SRB) assay. This type of cardiomyocytes death was mediated by the necrosis pathway rather than apoptosis, as determined by using flow cytometry to characterize the mode of dasatinib-induced cell death. Inhibition of receptor-interacting protein kinase 1 (RIP1)activity and knockdown of receptor-interacting protein kinase 3 (RIP3)expression can block dasatinib-evoked cardiotoxicity, which further confirmed the involvement of necroptosis. We next found that the classic substrates of RIP3, mixed lineage kinase domain-like protein (MLKL) and Ca2+-calmodulin-dependent protein kinase II (CaMKII) were not involved in dasatinib-induced cardiomyocytes necroptosis. What's more, unlike the inflammation-associated necroptosis, dasatinib-triggered necroptosis was dependent on intracellular instead of secreted High-mobility group box 1 (HMGB1) protein. Collectively, our study revealed that dasatinib-induced cardiotoxicity acted via leading cardiomyocytes to HMGB1-mediated necroptosis, indicating a viable strategy for prevention of dasatinib-induced cardiotoxicity.

Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study.

BACKGROUND: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. AIMS: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. METHODS: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. RESULTS: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P<0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P=0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P=0.033). CONCLUSIONS: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer.

Proteomic Profiling of Neuroblastoma Cells Adhesion on Hyaluronic Acid-Based Surface for Neural Tissue Engineering.

The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application.

Nucleoporin 62 and Ca(2+)/calmodulin dependent kinase kinase 2 regulate androgen receptor activity in castrate resistant prostate cancer cells.

BACKGROUND: Re-activation of the transcriptional activity of the androgen receptor (AR) is an important factor mediating progression from androgen-responsive to castrate-resistant prostate cancer (CRPC). However, the mechanisms regulating AR activity in CRPC remain incompletely understood. Ca(2+) /calmodulin-dependent kinase kinase (CaMKK) 2 was previously shown to regulate AR activity in androgen-responsive prostate cancer cells. Our objective was to further explore the basis of this regulation in CRPC cells. METHODS: The abundance of CaMKK2 in nuclear fractions of androgen-responsive prostate cancer and CRPC, cells were determined by subcellular fractionation and Western blotting. CaMKK2 association with nuclear pore complexes (NPCs) and nucleoporins (Nups) including Nup62, were imaged by structured illumination and super-resolution fluorescence microscopy and co-immunoprecipitation, respectively. The abundance and subcellular localization of CaMKK2 and Nup62 in human clinical specimens of prostate cancer was visualized by immunohistochemistry. The role of Nups in the growth and viability of CRPC cells was assessed by RNA interference and cell counting. The involvement of CaMKK2 and Nup62 in regulating AR transcriptional activity was addressed by RNA interference, chromatin immunoprecipitation, androgen response element reporter assay, and Western blotting. RESULTS: CaMKK2 was expressed at higher levels in the nuclear fraction of CPRC C4-2 cells, than in that of androgen-responsive LNCaP cells. In C4-2 cells, CaMKK2 associated with NPCs of the nuclear envelope and physically interacted with Nup62. CaMKK2 and Nup62 demonstrated pronounced, and similar increases in both expression and perinuclear/nuclear localization in human clinical specimens of advanced prostate cancer relative to normal prostate. Knockdown of Nup62, but not of Nups, 98 or 88, reduced growth and viability of C4-2 cells. Knockdown of Nup62 produced a greater reduction of the growth and viability of C4-2 cells than of non-neoplastic RWPE-1 prostatic cells. Nup62, CaMKK2, and the AR were recruited to androgen response elements of the AR target genes, prostate specific antigen, and transmembrane protease, serine 2. Knockdown of CaMKK2 and Nup62 reduced prostate specific antigen expression and AR transcriptional activity driven by androgen response elements from the prostate-specific probasin gene promoter. CONCLUSION: Nup62 and CaMKK2 are required for optimal AR transcriptional activity and a potential mechanism for AR re-activation in CRPC.

Structural characterization of altered nucleoporin Nup153 expression in human cells by thin-section electron microscopy.

Nuclear pore complexes (NPCs) span the 2 membranes of the nuclear envelope (NE) and facilitate nucleocytoplasmic exchange of macromolecules. NPCs have a roughly tripartite structural organization with the so-called nuclear basket emanating from the NPC scaffold into the nucleoplasm. The nuclear basket is composed of the 3 nucleoporins Nup153, Nup50, and Tpr, but their specific role for the structural organization of this NPC substructure is, however, not well established. In this study, we have used thin-section transmission electron microscopy to determine the structural consequences of altering the expression of Nup153 in human cells. We show that the assembly and integrity of the nuclear basket is not affected by Nup153 depletion, whereas its integrity is perturbed in cells expressing high concentrations of the zinc-finger domain of Nup153. Moreover, even mild over-expression of Nup153 is coinciding with massive changes in nuclear organization and it is the excess of the zinc-finger domain of Nup153 that is sufficient to induce these rearrangements. Our data indicate a central function of Nup153 in the organization of the nucleus, not only at the periphery, but throughout the entire nuclear interior.

Cell-fusion method to visualize interphase nuclear pore formation.

In eukaryotic cells, the nucleus is a complex and sophisticated organelle that organizes genomic DNA to support essential cellular functions. The nuclear surface contains many nuclear pore complexes (NPCs), channels for macromolecular transport between the cytoplasm and nucleus. It is well known that the number of NPCs almost doubles during interphase in cycling cells. However, the mechanism of NPC formation is poorly understood, presumably because a practical system for analysis does not exist. The most difficult obstacle in the visualization of interphase NPC formation is that NPCs already exist after nuclear envelope formation, and these existing NPCs interfere with the observation of nascent NPCs. To overcome this obstacle, we developed a novel system using the cell-fusion technique (heterokaryon method), previously also used to analyze the shuttling of macromolecules between the cytoplasm and the nucleus, to visualize the newly synthesized interphase NPCs. In addition, we used a photobleaching approach that validated the cell-fusion method. We recently used these methods to demonstrate the role of cyclin-dependent protein kinases and of Pom121 in interphase NPC formation in cycling human cells. Here, we describe the details of the cell-fusion approach and compare the system with other NPC formation visualization methods.

Mitigation of postischemic cardiac contractile dysfunction by CaMKII inhibition: effects on programmed necrotic and apoptotic cell death.

While Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been suggested to be an important protein regulating heart function upon ischemia/reperfusion (I/R), the mechanisms responsible are not fully known. Furthermore, it is not known whether CaMKII activation can modulate necroptosis, a recently described form of programmed cell death. In order to investigate these issues, Langendroff-perfused rat hearts were subjected to global ischemia and reperfusion, and CaMKII inhibition was achieved by adding the CaMKII inhibitor KN-93 (0.5 µmol/dm(3)) to the perfusion solution before the induction of ischemia. Immunoblotting was used to detect changes in expression of proteins modulating both necroptotic and apoptotic cell death. CaMKII inhibition normalized I/R induced increases in expression of necroptotic RIP1 and caspase-8 along with proteins of the intrinsic apoptotic pathway, namely cytochrome c and caspase-9. In addition, it increased the Bcl-2/Bax ratio and reduced caspase-3 and cleaved PARP1 content suggesting reduction of cell death. These changes coexisted with improvement of postischemic contractile function. On the other hand, there was no correlation between levels of pT287-CaMKIIδ and LVDP recovery after I/R. These results demonstrate for the first time that CaMKII inhibition may mitigate cardiac contractile dysfunction, at least partially, by limiting the contents of not only apoptotic, but also necroptotic proteins. Phosphorylation of CaMKII seems unlikely to determine the degree of postischemic recovery of contractile function.

Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer.

Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.

Changing subcellular localization of nuclear transport factors during human spermatogenesis.

Spermatogenesis requires progressive changes in gene expression mediated by hormonal and local factors. Regulated macromolecular movement between nuclear and cytoplasmic compartments enables these essential responses to changing extracellular cues, and dynamic production of the nucleocytoplasmic transporters and importin proteins, throughout gametogenesis in rodents implicates them as key mediators of germline differentiation. We examined normal adult human testis expression profiles of six importins plus five additional proteins involved in nucleocytoplasmic transport. Although most were detected in the nucleus during germline differentiation, importin α4 was exclusively observed in Sertoli and germ cell cytoplasm. Many proteins were present in round spermatid nuclei (importins α1, α3, ß1, ß3; exportin-1, Nup62, Ran, RanBP1, RCC1), and remarkable intense nuclear and/or nuclear-associated signals were detected for importin α1, importin α3 and Nup62 in spermatocytes. This study identifies conserved aspects of nucleocytoplasmic transport during spermatogenesis and extends our knowledge of the dynamic presence of these proteins, which indicates that they contribute to germ cell-specific cargo trafficking and potentially to other functions during human spermatogenesis. We also demonstrate for the first time that importin α3 is nuclear in spermatocytes, when exportin-1 is cytoplasmic, suggesting that nuclear transport is altered during meiosis.

Nup88 expression is associated with myometrial invasion in endometrial carcinoma.

BACKGROUND: The nuclear pore complex protein Nup88 has been shown in previous studies to be overexpressed in tumor cells and to be associated in breast cancer with all clinical and biological features defining a more aggressive phenotype. METHODS: In this pilot study, Nup88-mRNA expression was studied in a series of 29 endometrial carcinomas, of which 27 belonged to the endometrioid variety, the remaining 2 being papillary serous tumors, to verify if Nup88 plays a similar role in endometrial carcinoma as the one described in breast cancer. The tumor samples were obtained directly at the operating suite and fresh frozen at the time of hysterectomy. Nup88-mRNA expression was studied in them by means of differential reverse transcriptase-polymerase chain reaction. Nup88-mRNA expression was correlated with the clinical features of the tumors. RESULTS: A significant correlation (r = 0.41, P = 0.027) was found between growing levels of Nup88-mRNA expression and depth of myometrial invasion. There was no correlation between Nup88-mRNA expression and the other 2 available clinical parameters, that is, tumor grade (r = 0.05, P = 0.79) and surgical stage (r = -0.18, P = 0.34). CONCLUSIONS: From these results, it is concluded that Nup88 expression seems indeed to be associated with a distinct feature of tumor aggressiveness (myometrial invasion) in endometrial carcinoma and that larger studies are therefore probably worthwhile.

Nup88 mRNA overexpression in colorectal cancers and relationship with p53.

OBJECTIVES: We measured nucleoporin 88 (Nup88) mRNA expression in primary colorectal cancers to investigate its relationship with clinicopathological features and p53. METHODS: The primary cancer tissues, adjacent noncancerous tissues and the proximal and distant margins of normal mucosa were collected from 73 colorectal cancer patients during surgery. Nup88 mRNA expression was measured on these fresh specimens and on colon cell lines HCT-116^{p53 + / + } and HCT-116^{p53 - / - } by RT-PCR while p53 mRNA and ß-actin as controls. Nup88 and p53 protein expression were then immunohistochemistrically examined in other 25 colorectal cancers specimens paraffin embedded and formalin fixed. RESULTS: Nup88 expression was higher in primary cancer tissues than in adjacent noncancerous tissues, and in the proximal and distant margins of normal mucosa. Overexpression of Nup88 mRNA was statistically associated with TNM stage (P=0.044), lymphatic metastasis (P=0.022), and cancer location (P=0.036), while not related to gender, age of patients and histological type, infiltration depth, and differentiation of cancers. The expression of Nup88 mRNA in the HCT-116^{p53 - / - } cell line was not significantly different from expression in the HCT-116^{p53 + / +}cell line. And there was no correlation between Nup88 and p53 protein expression (r=0.632, P=0.368). CONCLUSIONS: Nup88 mRNA was overexpressed in colorectal cancers and the overexpression was associated with cancer development and aggressiveness. Nup88 might be regard as essential contributor to nodal metastagenicity of colorectal cancer.

Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines.

PURPOSE: RanBP2 is a small ubiquitin-like modifier ligase for DNA topoisomerase II (TopoII) and plays a role in maintaining chromosome stability by recruiting TopoII to centromeres during mitosis. Engineered-mice with low amounts of RanBP2 have been reported to form lung adenocarcinomas. Furthermore, in the murine embryonic fibroblasts, formation of chromatin bridges in anaphase, a distinctive feature of cells with impaired DNA decatenation by chemical inhibition of TopoII, has been reported. In this study, we tested whether the association between mRNA expression of the RanBP2 gene and chemosensitivity of a TopoII inhibitor, amrubicin could be seen. METHODS: Using a panel of 20 lung cancer cell lines, the mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes were examined by quantitative real-time reverse transcription PCR. The in vitro cytotoxicity of amrubicin was assessed using a tetrazolium-based colorimetric assay (MTT assay). RESULTS: Although RanBP2 mRNA expression was infrequently downregulated in human lung cancer cell lines, significantly higher RanBP2 transcripts were observed in small cell lung cancer than non-small cell lung cancer. There were no correlations between chemosensitivity of amrubicin and mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes. CONCLUSIONS: Our in vitro results suggest that mRNA expressions of RanBP2 and TopoII isoforms are unlikely to be a predictive biomarker for the sensitivity to amrubicin.

Involvement of regulations of nucleophosmin and nucleoporins in gambogic acid-induced apoptosis in Jurkat cells.

Gambogic acid, the main active compound of gamboge resin of Garcinia hanburryi, has recently exhibited marked antitumour potency on solid tumours of various derivations. We demonstrate here that gambogic acid also present powerful antileukaemic potency through both growth arrest and apoptosis induction in Jurkat cells, which was accompanied by typical apoptotic morphological changes and sharp decreased expression of Bcl-xL and Bcl-2. Furthermore, nucleophosmin, recently demonstrated to be mutated and aberrantly localized in the cytoplasm of leukaemia blasts in a high proportion of patients with acute myeloid leukaemia, was over-expressed in Jurkat cells. As the sole site of nucleocytoplasmic communication, the protein components of nuclear pore complex, such as NUP98, NUP88, NUP214 complex, were also deregulated in Jurkat cells. Especially, NUP98 was found to distribute mainly at the cell membrane, while NUP88 and NUP214 situated not just at the nuclear envelope, but also in the cytoplasm. However, in vitro treatment with gambogic acid resulted in significantly reduced expression of nucleophosmin and all three nucleoporins in a dose-dependent manner. Moreover, most of NUP88 and NUP214 nucleoporins were relocated to the nuclear rim in the gambogic acid-treated cells. These results suggest that the fact that nucleophosmin and some nucleoporins might act as new targets of gambogic acid, correlates well with the sensitivity to gambogic acid, as well as the rate of apoptosis induced by gambogic acid. Mechanisms that regulate nucleocytoplasmic transport of proteins may provide novel opportunities for drug development.

Bax expression in untreated breast cancer: an immunocytometric study of 255 cases.

BACKGROUND: Bax is one of the main effectors of apoptosis in breast cancer. However, in contrast with the antiapoptotic protein Bcl-2, which has been extensively studied in this tumor, there are relatively few clinical studies on the biological role of Bax in breast cancer. MATERIALS AND METHODS: The expression of the apoptosis-related Bax gene was studied in a series of 255 previously untreated breast cancers by means of immuno-flow cytometry. Additionally, and by the same method, the expression of the Bcl-2, VEGF and Nup88 genes were also studied. As variables of the study for the final statistical analysis, the histological variety of the tumors, histological and nuclear grade, the expression of hormone receptors, p53, Ki-67 or c-erb-B2, axillary node invasion, tumor size and DNA-ploidy were also included. RESULTS: The expression of the proapoptotic Bax protein was significantly associated with the expression of Nup88 (p<0.0001), VEGF (p=0.0014) and Bcl-2 (p=0.0063), all measured by the same method. An inverse correlation with c-erb-B2 expression, which almost attained statistical significance (p=0.058) was also registered. CONCLUSION: This study adds evidence to the little explored link between apoptosis and angiogenesis. Furthermore, it discloses a previously unreported relationship between Bax and Nup88 expression.

[Effect of deguelin on expression of nup98 in K562 cells].

The study was purposed to investigate the effect of deguelin on expression of nucleoporin 98 (nup98) in leukemia K562 cells. MTT assay was used to assess the effects of deguelin on cell proliferation. FCM and RT-PCR were used to analyze the changes of nup98 mRNA and protein in K562 cells after treating with deguelin. The results showed that deguelin inhibited the proliferation of K562 cells in a time- and dose-dependent manner; mean fluorescence intensity of nup98 in blank group (34.22 +/- 1.63) was significantly higher than that in control group (2.83 +/- 0.02, P < 0.01), 10 nmol/L deguelin could significantly inhibit the expression of nup98 protein; 10 nmol/L could not inhibit the expression of nup98 mRNA, 20, 40, 80, 160 nmol/L deguelin could significantly inhibit the expression of nup98 mRNA in a dose-dependant manner. It is concluded that deguelin inhibits the proliferation of K562 cell through inhibiting the expression of nup98, and may be considered as a new target for therapy of acute leukemia.