Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple promoters and differential splicing of 5' upstream exons are often found in various nuclear receptor genes including steroid receptors. Three promoters control the expression of human estrogen receptor alpha (ERalpha) isoforms: ERalpha-A, ERalpha-B, and ERalpha-C, and two promoters control the expression of human progesterone receptor (PR) isoforms: PR-A and PR-B. The expression levels of these isoforms differ with respect to each other in certain target tissues. The role of these isoforms may differ in various types of cells and tissues. The ER and PR contain CpG islands in the 5' upstream regions. One possible mechanism for changing the transcriptional status is methylation of CpG-enriched regions in these isoforms. We have investigated the expression and methylation status of the three different ERalpha promoters and the two different PR gene promoters by using methylation specific PCR (MSP) and direct DNA sequencing in several endometrial and prostate cancer cell lines and tissues. The results of these experiments suggest that ERalpha-A, ERalpha-B, and PR-A were expressed and ERalpha-C and PR-B were inactivated in endometrial cancers. To the contrary, ERalpha-A and ERalpha-B were inactivated and ERalpha-C, PR-A and PR-B were expressed in all prostate cancer. Treatment with demethylating agent (5-aza-2'-deoxycytidine) restored these gene expressions, suggesting that inactivation of this gene is through methylation. Our MSP and direct DNA sequencing showed that ERalpha-A, ERalpha-B, and PR-A genes were unmethylated and ERalpha-C and PR-B were methylated in endometrial cancers although ERalpha-A and ERalpha-B were methylated and ERalpha-C, PRA and PRB were unmethylated in prostate cancers. These reports clearly demonstrate that selective hypermethylation can selectively silence multiple promoters of steroid receptors in carcinogenesis.
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PMID:Hypermethylation can selectively silence multiple promoters of steroid receptors in cancers. 1277 Jul 52

Previous studies showed that progesterone receptor (PR), one of the hormone receptor superfamily, was only connected with the sex-correlated cancers such as breast cancer, endometrial cancer, prostate cancer, etc. This article deals with the PR gene in leukemia. We investigated the methylation status and the expression of the two different PR isoforms, PRA and PRB, in three leukemia cancer cell lines using methylation-specific polymerase chain reaction (MSP-PCR) and reverse transcription-PCR. The correlation of PR methylation and expression together with DNA methyltransferase (DNMT1) was further studied. We found that DNMT1 is required to maintain CpG methylation and aberrant gene silencing of PR gene in human leukemia cancer cells. The activity of 5-aza-2'-deoxycytidine in demethylation and gene reactivation may be through depleting cellular DNMT1 levels. In addition, extensive methylation of PRA and PRB was also observed in leukemia samples. Our results suggest that PR CpG island aberrant hypermethylation could be one molecular and genetic alteration in leukemia.
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PMID:Progesterone receptor gene inactivation and CpG island hypermethylation in human leukemia cancer cells. 1517 46