Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis.
Hypermethylation of regulatory sequences at the locus of the pi-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.
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
W H
WH
Lee
R A
RA
Morton
J I
JI
Epstein
J D
JD
Brooks
P A
PA
Campbell
G S
GS
Bova
W S
WS
Hsieh
W B
WB
Isaacs
W G
WG
Nelson
D002277:Carcinoma / Q000201:enzymology*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008745:Methylation; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping
D012333:RNA, Messenger; D003562:Cytidine; D005982:Glutathione Transferase; D004264:DNA Topoisomerases, Type I; C016568:5-methylcytidine