Methylation of the CD44 metastasis suppressor gene in human prostate cancer

Previous studies demonstrated that CD44 is a metastasis suppressor gene for prostate cancer and that the expression of CD44 both at mRNA and protein l evels is down-regulated during prostate cancer progression, with down-regul ation being correlated with higher tumor grade, aneuploidy, and distant met astasis, In this study, we evaluated DNA hypermethylation as a potential me chanism accompanying this decreased CD44 expression in human prostate cance r. Nucleotide sequence analysis revealed a CpG island in the CD44 transcrip tional regulatory region. We found that cytosine methylation of CD44 promot er 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 g ene. In addition, we examined methylation status of CD44 in 84 matched norm al 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 prosta te cancer, and 4 of the 40 matched normal tissues. These results demonstrat ed 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.