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)

Rb2/p130 is a member of the retinoblastoma family of proteins, consisting of Rb, Rb2 and p107, which are important negative regulators of cell cycle progression and differentiation. While Rb2 downregulation was observed in several malignant tumours including endometrial cancer, the role of p130 in breast carcinomas is still unknown. We investigated Rb2 protein expression in tumour tissue from 68 mammary and 41 endometrial carcinomas, 4 mammary cell lines, and normal tissue samples. Therefore, we performed Western blot experiments for Rb2, Rb, and the oestrogen and progesterone receptors (ER, PR-A, PR-B). Weak or absent Rb2 expression was more often found in endometrial (59%) than in mammary carcinomas (24%). We found significant positive correlations of Rb2 expression with Rb, ER, and PR-B in breast cancer samples, and of Rb2 with Rb, PR-A, PR-B, and younger age in endometrial carcinomas. No significant associations with histological grading, stage, nodal involvement, or Ki67 staining were detected. Rb2 mRNA expression was studied by semi-quantitative RT-PCR in 56 endometrial or mammary tissue samples and correlated significantly with Western blot results. Our results indicate that loss of Rb2 expression, mostly by transcriptional down-regulation, may be associated with the development and dedifferentiation of most endometrial and a subset of mammary carcinomas.
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PMID:Expression of Rb2/p130 in breast and endometrial cancer: correlations with hormone receptor status. 1150 94

Tamoxifen, a selective estrogen modulator (SERM) that has found clinical utility in the treatment of breast cancer, is an antagonist in the breast and an agonist in the uterus. These agonist actions in the uterus lead to an increased risk of endometrial cancer. In this study in mice we have analyzed the mechanism of action of tamoxifen in inducing cell proliferation in the uterine luminal epithelia. Tamoxifen induces a wave of DNA synthesis in these epithelial cells with kinetics similar to those seen after 17beta-estradiol (E(2)) treatment. However, by these criteria of mitogenicity, it is much less potent and never achieves full estrogenicity. This uterine epithelial cell proliferation is preceded by the mobilization of cyclin D1 from the cytoplasm to the nucleus which, together with CDK4, phosphorylates members of the Rb-retinoblastoma family of proteins, pRb and p107. Subsequent to this initial nuclear accumulation of cyclin D1, cyclin E and then cyclin A are induced that, together with the activation of CDK2, results in enhanced cyclin E- and cyclin A-dependent CDK2 kinase activity and further phosphorylation of pRb and p107. These actions of tamoxifen parallel those of E(2). Tamoxifen also induced the classical estrogen water imbibition response. However, in this it was more potent, producing a maximal response at doses that do not affect DNA synthesis. This suggests that the uterotropic response is not an accurate predictor of the compound's hyperplasia responses. We can conclude that, in its effects on proliferation, tamoxifen acts as a classical impeded estrogen and this suggests that the AF-1 transcription activation domain of the estrogen receptor that is activated upon both E(2) and tamoxifen binding to this receptor regulates these responses in the uterus.
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PMID:The molecular basis of tamoxifen induction of mouse uterine epithelial cell proliferation. 1564 90

The retinoblastoma family consists of the tumor suppressor nuclear phosphoprotein pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in lung and endometrial cancer and choroidal melanomas show a tight inverse correlation between the histologic grading in the most aggressive tumor types and pRb2/p130 expression. This led us to investigate the role of pRb2/p130 in salivary tumors. We studied the expression of pRb2/p130, p107, E2F4, p27, and PcNA by immunohistochemistry in a panel of 44 salivary gland tumors. We found a direct correlation between the cytoplasmic expression of pRb2/p130 and tumor grading and the presence of metastasis that was highly statistically significant (P < 0.001). Additionally, increased cytoplasmic pRb2/p130 expression was significantly correlated with a decreased probability of survival (P < 0.001). Interestingly, p107 nuclear expression showed a strong direct correlation when compared with the same variables. pRb2/p130 showed the highest percentage of undetectable nuclear levels in the specimens examined and the tightest inverse correlation (P < 0.0001) with both the histologic grading and pCNA expression in malignant salivary tumors. Additionally, E2F4 showed an identical localization pattern as to that of pRb2/p130. These data suggests an important role for pRb2/p130 in the pathogenesis and progression of certain salivary gland cancers.
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PMID:Expression of cell cycle-regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA in salivary gland tumors: prognostic and diagnostic implications. 1586 22