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 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 who 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.
Lou
W
W
Department of Pathology and Cancer Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Krill
D
D
Dhir
R
R
Becich
M J
MJ
Dong
J T
JT
Frierson
H F
HF
Isaacs
W B
WB
Isaacs
J T
JT
Gao
A C
AC
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins