Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen receptors (ERs) regulate the transcription of genes involved in breast cancer cell proliferation, invasion and metastasis. In addition to ligand concentration, phosphorylation and coactivator/corepressor levels control ER-dependent transcription. In this study, we used MCF-7 breast cancer sublines with variable levels of the steroid receptor coactivator 1 (SRC-1) to investigate the importance of coactivator levels in basal and estrogen-inducible expression of SDF-1alpha/CXCL12, cathepsin D and cMyc. Basal expression of SDF-1alpha and cMyc but not of cathepsin D was substantially lower in a MCF-7 subline lacking SRC-1 ((MCF-7/p2) compared with MCF-7 sublines expressing SRC-1 (MCF-7/p1 and LCC2). Although estrogen efficiently induced SDF-1alpha in MCF-7/p1 cells, very little induction of this gene was observed in MCF-7/p2 cells. The absence of SRC-1 had no effect on estrogen-inducible expression cMyc and cathepsin D suggesting that coactivator levels determine the expression of only a subset of estrogen-regulated genes. Introduction of SRC-1, SRC-2/TIF-2 or SRC-3/AIB1 increased basal expression of SDF-1alpha in MCF-7/p2 cells. Consistent with the role of SDF-1alpha in mediating estrogen-induced proliferation, estrogen failed to increase proliferation of MCF-7/p2 cells. In matrigel invasion assays, conditioned media from MCF-7/p1 but not MCF-7/p2 cells increased invasion of cancer cells expressing metastasis-associated genes and CXCR4, the receptor for SDF-1alpha. These results suggest that coactivators control SDF-1alpha expression, which mediates estrogen-induced proliferation and invasion through autocrine and paracrine mechanisms, respectively. These results also provide a molecular explanation for recent observations linking co-overexpression of coactivators and her2/neu with poor prognosis: coactivators increase SDF-1alpha expression whereas her2/neu stabilize CXCR4 protein.
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PMID:The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1alpha/CXCL12. 1591 9

The aim of the study was to test the hypothesis that expression of retinoid receptors (RARalpha, RARbeta, RARgamma), rexinoid receptors (RXRalpha, RXRbeta), thyroid hormone receptors (TRalpha, TRbeta), estrogen receptors (ERalpha, ERbeta), nuclear receptor coregulators (N-CoR, SRC-1, SMRT), and in addition type I iodothyronine 5'-deiodinase (5'-DI), EGFR and erb-B2/neu would be different in mammary postlactating tissue in comparison with that of nonlactating mammary gland. Using RT-PCR, we have shown that expression of RARalpha, RXRalpha,TRalpha, ERalpha,ERbeta,N-CoR, SRC-1, SMRT and EGFR in rat was significantly increased in postlactating mammary gland when compared to that of nonlactating mammary tissue. Postlactating mammary glands were found to express all RAR and RXR subtypes studied when compared to nonlactating mammary tissues that express exclusively RARalpha and RXRalpha subtypes. Enhanced expression of a number of nuclear hormone receptors, their coregulators in mammary tissue of postlactating rats in comparison with nonlactating animals identify a potential role for retinoid, thyroid and estrogen signalling pathways also after lactation period.
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PMID:Expression of nuclear hormone receptors, their coregulators and type I iodothyronine 5'-deiodinase gene in mammary tissue of nonlactating and postlactating rats. 1594 93

Endocrine therapy for advanced prostate cancer is based on androgen ablation or blockade of the androgen receptor (AR). AR action in prostate cancer has been investigated in a number of cell lines, their derivatives, and transgenic animals. AR expression is heterogenous in prostate cancer in vivo; it could be detected in most primary tumors and their metastases. However, some cells lack the AR because of epigenetic changes in the gene promoter. AR expression increases after chronic androgen ablation in vitro. In several xenografts, AR upregulation is the most consistent change identified during progression towards therapy resistance. In contrast, the AR pathway may be by-passed during chronic treatment with a nonsteroidal anti-androgen. AR sensitivity in prostate cancer increases as a result of activation of the Ras/mitogen-activated protein kinase pathway. One of the major difficulties in endocrine therapy for prostate cancer is acquisition of agonistic properties of AR antagonists observed in the presence of mutated AR. Enhancement of AR function by associated coactivator proteins has been extensively investigated. Cofactors SRC-1, RAC3, p300/CBP, TIF-2, and Tip60 are upregulated in advanced prostate cancer. Most studies on ligand-independent activation of the AR are focused on Her-2/neu and interleukin-6 (IL-6). On the basis of studies that showed overexpression and activation of the AR in advanced prostate cancer, it was suggested that novel therapies that reduce AR expression will provide a benefit to patients. There is experimental evidence showing that prostate tumor growth in vitro and in vivo is inhibited following administration of chemopreventive drugs or antisense oligonucleotides that downregulate AR mRNA and protein expression.
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PMID:Androgen axis in prostate cancer. 1659 69