Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to search for novel estrogen-responsive genes, we performed serial analysis of gene expression (SAGE) for estrogen-treated MCF-7 human breast cancer cells. SAGE analysis of 31,000 and 30,856 tags from non-treated and 17 beta-estradiol (E2)-treated cells for 24 h, respectively, facilitated the identification of 15,037 different transcripts. Comparison of these two SAGE libraries indicated a remarkable similarity in expression profiles. Among the identified transcripts, four genes were found to be markedly increased for E2-treated cells compared with control cells. Three of the transcripts were cathepsin D, pS2 and high mobility group 1 protein, which have been described as estrogen-inducible genes. The fourth gene was WISP-2 (Wnt-1 inducible signaling pathway protein 2) which has recently been reported as an up-regulated gene in the mammary epithelial cell line C57 MG transformed by the Wnt-1 oncogene. The increase in WISP-2 mRNA was completely prevented by co-incubation with a pure anti-estrogen ICI 182,780, but not by coincubation with cycloheximide, indicating that WISP-2 is directly regulated by the estrogen receptor. The WISP-2 gene was also induced by treating with environmental estrogens, such as bisphenol-A or nonylphenol. This study represents the first comprehensive gene expression analysis of estrogen-treated human breast cancer cells.
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PMID:WISP-2 as a novel estrogen-responsive gene in human breast cancer cells. 1094 50

Recently, we identified WISP-2 (Wnt-1 inducible signaling pathway protein 2) as a novel estrogen-inducible gene in the MCF-7 human breast cancer cell line. In this study, we examined whether WISP-2 expression is modulated by PK activators. Treatment with protein kinase A (PKA) activators [cholera toxin plus 3-isobutyl-1-methylxanthine (CT/IBMX)] induced WISP-2 expression. CT/IBMX induced expression of the other estrogen-responsive gene, pS2, more dramatically than maximum stimulation by 17beta-estradiol (E2). Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), which directly stimulates protein kinase C (PKC) activity, completely prevented WISP-2 mRNA induction by E2, whereas it increased pS2 mRNA expression more dramatically than maximum stimulation by E2. Results of treatments with the protein synthesis inhibitor cycloheximide and the pure antiestrogen ICI182,780 suggest that these PK pathways modulate WISP-2 gene expression via different molecular mechanisms than those for pS2. Because TPA inhibits cell proliferation, we investigated whether WISP-2 induction was dependent on cell growth. Cells were treated with insulin-like growth factor-1 (IGF-1) or interleukin-1alpha (IL-1alpha) to stimulate or inhibit cell growth, respectively. These treatments had no effect on WISP-2 mRNA expression either alone or in combination with E2, suggesting that WISP-2 induction is independent of cell growth.
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PMID:Estrogen-induced genes, WISP-2 and pS2, respond divergently to protein kinase pathway. 1295 Oct 45

Estrogen receptors (ER) are ligand-dependent transcription factors that regulate growth, differentiation, and maintenance of cellular functions in a wide variety of tissues. We report here that p21WAF1/CIP1, a cyclin-dependent kinase (Cdk) inhibitor, cooperates with CBP to regulate the ERalpha-mediated transcription of endogenous target genes in a promoter-specific manner. The estrogen-induced expression of the progesterone receptor and WISP-2 mRNA transcripts in MCF-7 cells was enhanced by p21WAF1/CIP1, whereas that of the cyclin D1 mRNA was reduced and the pS2 mRNA was not affected. Chromatin immunoprecipitation assays revealed that p21WAF1/CIP1 was recruited simultaneously with ERalpha and CBP to the endogenous progesterone receptor gene promoter in an estrogen-dependent manner. Experiments in which the p21WAF1/CIP1 protein was knocked down by RNA interference showed that the induction of the expression of the gene encoding the progesterone receptor required p21WAF1/CIP1, in contrast with that of the cyclin D1 and pS2 genes. p21WAF1/CIP1 induced not only cell cycle arrest in breast cancer cells but also milk fat globule protein and lipid droplets, indicators of the differentiated phenotype, as well as cell flattening and increase of the volume of the cytoplasm. These results indicate that p21WAF1/CIP1, in addition to its Cdk-regulatory role, behaves as a transcriptional coactivator in a gene-specific manner implicated in cell differentiation.
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PMID:p21WAF1/CIP1 selectively controls the transcriptional activity of estrogen receptor alpha. 1574 34