Cytidine methylation of regulatory sequences near the π-class glutathione S-transferase gene accompanies human prostatic carcinogenesis

Wen Hsiang Lee, Ronald A. Morton, Jonathan I. Epstein, James D. Brooks, Pearl A. Campbell, G. Steven Bova, Wen Son Hsieh, William B. Isaacs, William G. Nelson

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Abstract

Hypermethylation of regulatory sequences at the locus of the π-class glutathione S-transferase gene GSTP1 was detected in 20 of 20 human prostatic carcinoma tissue specimens studied but not in normal tissues or prostatic tissues exhibiting benign hyperplasia. In addition, a striking decrease in GSTP1 expression was found to accompany human prostatic carcinogenesis. Immunohistochemical staining with anti-GSTP1 antibodies failed to detect the enzyme in 88 of 91 prostatic carcinomas analyzed. In vitro, GSTP1 expression was limited to human prostatic cancer cell lines containing GSTP1 alleles with hypomethylated promoter sequences; a human prostatic cancer cell line containing only hypermethylated GSTP1 promoter sequences did not express GSTP1 mRNA or polypeptides. Methylation of cytidine nucleotides in GSTP1 regulatory sequences constitutes the most common genomic alteration yet described for human prostate cancer.

Original languageEnglish (US)
Pages (from-to)11733-11737
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number24
DOIs
StatePublished - Nov 22 1994

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