DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer.
The retinoblastoma protein-interacting zinc finger gene, RIZ1, is thought to be a tumor suppressor gene. RIZ1 is inactivated by mutation, deletion and DNA methylation in several human cancers. In the present study, the relationship between DNA methylation of RIZ1 and mutation of p53 was investigated in prostate cancer (PCa). In total, 47 cases of node-negative PCa (stages I-III) were analyzed. DNA methylation of the RIZ1 gene was detected in 20 (42.6%) of the 47 PCa tissues by methylation-specific polymerase chain reaction. DNA methylation of the RIZ1 gene was not associated with clinicopathological features. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score (16/30, 53.3%) than in those with a low Gleason score (4/17, 23.5%); however, this tendency was not statistically significant (P = 0.0675). Nuclear accumulation of p53 was observed in four (8.5%) of 47 PCa specimens by immunostaining. All four PCa specimens with nuclear accumulation of p53 were stage III disease and showed DNA methylation of RIZ1. However, of the remaining 43 cancers without nuclear accumulation of p53, DNA methylation of RIZ1 was observed in only 16 (37.2%) specimens (P = 0.0272). Of the three PCa cell lines, only the PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis. Genetic alterations are likely associated with epigenetic alterations in PCa.
Hasegawa
Yasuhisa
Y
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima 734-8551, Japan.
Matsubara
Akio
A
Teishima
Jun
J
Seki
Mitsuhiro
M
Mita
Koji
K
Usui
Tsuguru
T
Oue
Naohide
N
Yasui
Wataru
W
D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human