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

In this paper, we confirmed that retinoic acid is an antiestrogenic compound with respect to different chimaeric estrogenic responses and with respect to different cellular types. This was shown by transient transfection of MCF-7 cells with plasmids driving the chloramphenicol acetyl-transferase gene via different estrogenic regulatory part (pS2) and the first promotor of the progesterone receptor gene (PR1); an identical conclusion was obtained in HeLa cells by cotransfecting a plasmid expressing the estrogen receptor. In addition, the inhibitory effect of retinoic acid was not observed for genes regulated by the progesterone receptor and the glucocorticoid receptor. As the antiestrogenic effect of retinoic acid was increased by cotransfecting acid receptor(s) RAR alpha, beta, gamma, we concluded that RAR(s) is(are) involved in the antiestrogenic effect of retinoic acid.
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PMID:[Retinoic acid has an antiestrogenic effect on different regulated estrogen genes in different cellular types]. 182 92

The estrogen-receptor-related receptors (ERRs) alpha, beta, and gamma are orphan nuclear hormone receptors that share significant homology with the estrogen receptors (ERs) but are not activated by natural estrogens. In contrast, the ERRs display constitutive transcriptional activity in the absence of exogenously added ligand. However, the ERRs bind to the estrogen response element and to the extended half-sites of which a subset can also be recognized by ERalpha, suggesting that ERRs and ERs may control overlapping regulatory pathways. To test this hypothesis, we explored the possibility that ERRs could regulate the expression of the estrogen-inducible pS2 gene, a human breast cancer prognostic marker. Transfection studies show that all of the ERR isoforms can activate the pS2 promoter in a variety of cell types, including breast cancer cell lines. Surprisingly, sequence analysis combined with mutational studies revealed that, in addition to the well-characterized estrogen response element, the presence of a functional extended half-site within the pS2 promoter is also required for complete response to both ER and ERR pathways. We show that ERR transcriptional activity on the pS2 promoter is considerably enhanced in the presence of all three members of the steroid receptor coactivator family but is completely abolished on treatment with the synthetic estrogen diethylstilbestrol, a recently described inhibitor of ERR function. Finally, we demonstrate that ERRalpha is the major isoform expressed in human breast cancer cell lines and that diethylstilbestrol can inhibit the growth of both ER-positive and -negative cell lines. Taken together, these results demonstrate that estrogen-inducible genes such as pS2 can be ERR targets and suggest that pharmacological modulation of ERRalpha activity may have therapeutic value in the treatment of breast cancer.
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PMID:Transcriptional regulation of the estrogen-inducible pS2 breast cancer marker gene by the ERR family of orphan nuclear receptors. 1155 47