Methylation of the 5' CpG island of the endothelin B receptor gene is common in human prostate cancer

Joel B. Nelson, Wen Hsiang Lee, Son H. Nguyen, David F. Jarrard, James D. Brooks, Scott R. Magnuson, Terry J. Opgenorth, William G. Nelson, G. Steven Bova

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Production of the potent vasoconstrictor endothelin-1 (ET-1) by human prostate cancer cells accompanies prostate cancer progression in vivo. The predominant endothelin receptor expressed by normal prostate epithelium, ET(B), is not expressed by any of the established human prostate cancer cell lines, and ET(B) binding is decreased on prostate cancer tissues. ET(B), which may mediate ET-1 clearance and may inhibit ET-1 secretion, is encoded by a gene that contains a 5' CpG island encompassing the transcriptional regulatory region. We examined this regulatory region of the ET(B) receptor gene (EDNRB) in determine whether hypermethylation of cytidine nucleotides accompanies decreased ET(B) expression in human prostate cancer. We found somatic methylation of CpG island sequences in EDNRB in 5 of 5 human prostate cancer cell lines, 15 of 21 primary prostate cancer tissues, and 8 of 14 prostate cancer metastases (70% of samples overall). Normal tissues contained only unmethylated EDNRB. Treatment of human prostatic carcinoma cell line cultures with 5-azacytidine induced ET(B) mRNA expression, suggesting that CpG island methylation changes might accompany the apparent transcriptional silencing of EDNRB in vivo.

Original languageEnglish (US)
Pages (from-to)35-37
Number of pages3
JournalCancer Research
Volume57
Issue number1
StatePublished - 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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