Methylation of the CD44 metastasis suppressor gene in human prostate cancer

Wei Lou, Diane Krill, Rajiv Dhir, Michael J. Becich, Jin Tang Dong, Henry F. Frierson, William B. Isaacs, John T. Isaacs, Allen C Gao

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Previous studies demonstrated that CD44 is a metastasis suppressor gene for prostate cancer and that the expression of CD44 both at mRNA and protein levels is down-regulated during prostate cancer progression, with down- regulation being correlated with higher tumor grade, aneuploidy, and distant metastasis. In this study, we evaluated DNA hypermethylation as a potential mechanism accompanying this decreased CD44 expression in human prostate cancer. Nucleotide sequence analysis revealed a CpG island in the CD44 transcriptional regulatory region. We found that cytosine methylation of CD44 promoter occurs in CD44-negative prostate cancer cell line (i.e., LNCaP) but not in prostate cancer cell lines (i.e., TSU, PC3, and DU145) expressing this gene. In addition, we examined methylation status of CD44 in 84 matched normal and cancer prostate specimens. Hypermethylation of the 5' CpG island of CD44 gene was observed in 31 of 40 primary prostate cancer specimens, 3 of 4 distant organ site metastases obtained at autopsy from men died of prostate cancer, and 4 of the 40 matched normal tissues. These results demonstrated that methylation of the 5' CpG island of CD44 gene is closely associated with transcriptional inactivation, resulting in a decreased expression of CD44 in human prostate cancer.

Original languageEnglish (US)
Pages (from-to)2329-2331
Number of pages3
JournalCancer Research
Volume59
Issue number10
StatePublished - May 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Lou, W., Krill, D., Dhir, R., Becich, M. J., Dong, J. T., Frierson, H. F., Isaacs, W. B., Isaacs, J. T., & Gao, A. C. (1999). Methylation of the CD44 metastasis suppressor gene in human prostate cancer. Cancer Research, 59(10), 2329-2331.