Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibins and activins are growth factors belonging to the transforming growth factor-beta) family and are known to influence cell proliferation and differentiation. Because transforming growth factor-beta is involved in physiological and tumoral changes of uterine tissues, the present study aimed to evaluate whether human normal and neoplastic endometrial and cervical epithelial cells express and secrete inhibin A, inhibin B, and activin A. To test this hypothesis, different approaches were used. By RT-PCR, the expression of specific messenger RNAs (mRNAs) for the inhibin alpha, activin betaA and betaB subunits, and activin receptor type II and type IIB was investigated: 1) in primary cultures of endometrial (stroma and epithelium) or cervical (epithelium) cells from healthy women; and 2) in specimens of endometrial or cervical carcinoma. To demonstrate a possible secretion of the proteins, dimeric inhibin A, inhibin B, and activin A were measured in culture medium of normal epithelial or stromal endometrial cells and in uterine washing fluid of healthy women or patients with endometrial adenocarcinoma. Levels of the proteins were also measured in serum of women with endometrial or cervical carcinoma. Cultured endometrial stromal or epithelial cells and epithelial cervical cells expressed inhibin alpha, activin betaA and betaB, and activin receptor type II and type IIB mRNAs. The same finding was obtained in specimens of endometrial or cervical carcinomas. Dimeric inhibin A, inhibin B, and activin A were measured in culture medium of both endometrial and cervical cells. In particular, resulting activin A levels were significantly higher in epithelial than in stromal cultured endometrial cells (P < 0.01). Dimeric proteins were also detected in the washing fluid of the uterine cavities of healthy women (controls) and with endometrial adenocarcinoma, in which higher activin A levels were found (P < 0.01 vs. controls). Women with endometrial carcinoma showed serum activin A levels significantly higher than healthy controls (P < 0.01), which significantly decreased after surgical removal of endometrial or cervical tumors (P < 0.01). The present study, for the first time, showed that inhibin A, inhibin B, and activin A, as well as activin receptors, are expressed in normal and neoplastic human uterine tissues. A secretion of activin A from tumoral cells into systemic circulation is suggested by the observation that the high levels in serum of patients with endometrial or cervical carcinoma decreased after the surgical removal of the tumor.
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PMID:Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. 954 40

Menstrual cycle-dependent expressions of activin A in normal human endometrial tissues have been reported. Expression of activin receptor mRNAs and increased activin A production were also observed in human endometrial adenocarcinoma tissues, suggesting that activin A might enhance cell proliferation and inhibit apoptotic signaling in endometrial cancer cells. In this study, we have examined the effects of activin A on cell proliferation, anticancer drug-induced apoptosis and Fas-mediated apoptosis in 3 differentiated human endometrial adenocarcinoma cell lines, namely HEC-1, HHUA and Ishikawa. Flow cytometric analyses revealed moderate expressions of all 4 types of activin receptor subunits on the cell surfaces of the 3 cell lines. The proliferations of the 3 endometrial cancer cells were completely unaffected by activin A, whereas it suppressed the cell proliferation of a human ovarian endometrioid adenocarcinoma cell line, OVK-18, in a dose-dependent manner. Moreover, activin A did not affect the apoptotic changes in the 3 endometrial adenocarcinoma cells treated with 4 different anticancer drugs, namely CDDP, paclitaxel, etoposide and SN38. The apoptotic changes in HHUA cells treated with anti-Fas IgM were also unaffected by activin A. These results indicate that the increased activin A production in human endometrial adenocarcinoma tissues in vivo may not stimulate carcinoma cell proliferation or inhibit apoptotic signaling in carcinoma cells. Insensitivity to the usual growth suppression signals induced by activin A might be one of the mechanisms of immortality of human endometrial adenocarcinoma cells.
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PMID:Expression and function of activin receptors in human endometrial adenocarcinoma cells. 1288 1

Although human endometrial adenocarcinoma tissues express high levels of activin A, the pathophysiological functions of endometrial activin A remain unclear. Human endometrial cancer cells express both activin receptor and TGF-beta receptor, and TGF-beta1 utilizes the same intracellular signaling molecules as activin A. Using three differentiated human endometrial adenocarcinoma cell lines, we investigated whether there are interactions between TGF-beta1- and activin A-mediated signaling. Flow cytometric analysis revealed cell surface expression of two types of TGF-beta receptor subunits and four types of activin receptor subunits. TGF-beta1 inhibited cell proliferation in three endometrial adenocarcinoma cell lines. Activin A did not affect the growth of the three endometrial cell lines, and pre-incubation with activin A dose-dependently reduced TGF-beta1-mediated inhibition of cell growth. These results suggest that in endometrial adenocarcinoma cells, the intracellular signals underlying TGF-beta1-mediated inhibition of growth can themselves be inhibited by activin A. Therefore, the increased expression of activin A may be involved in carcinogenesis by reducing TGF-beta-mediated signals inhibiting cell growth in human endometrial adenocarcinoma tissues.
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PMID:Activin A inhibits growth-inhibitory signals by TGF-beta1 in differentiated human endometrial adenocarcinoma cells. 1501 Aug 88