Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features.
EphA7 is a member of Eph/ephrins family and play diverse roles in carcinogenesis. The aim of our study was to investigate functional and structural alterations of EphA7 in prostate cancer and determine if those findings correlate with the clinicopathologic features of prostate cancer. Forty-eight prostate carcinomas, 31 benign prostate hyperplasias, 5 normal prostate tissues and 3 prostate cell lines (LNCaP, DU145 and PC-3) were examined with quantitative RT-PCR, methylation-specific PCR and immunohistochemistry. Downregulation or loss of EphA7 mRNA expression was detected in 23 of 48 (47.9%) prostate carcinomas, and 2 of 31 (6.5%) hyperplasias. Methylation of the EphA7 promoter region was present in 20 of 48 (41.7%) of carcinomas and 6 of 31 (19.3%) hyperplasias, respectively. Immunostaining analysis showed EphA7 protein was absent in 10 of 30 (33.3%) carcinoma samples available and 8 of them (80.0%) exhibited hypermethylation. The frequency of EphA7 methylation was higher in cancer patients with higher Gleason score. Treatment of DU145 cells harboring methylation with 5-aza-2'-deoxycytidine reactivated expression of EphA7. Ectopic expression of EphA7 in DU145 cells did not suppress cell growth but inhibited colony formation. Our study provides evidence that epigenetic inactivation of EphA7 may be involved in prostate carcinogenesis.
Guan
Ming
M
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, People's Republic of China. guanming88@yahoo.com
Xu
Chong
C
Zhang
Fanglin
F
Ye
Chuanzhong
C
D000368:Aged; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D036141:Receptor, EphA7 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D036141:Receptor, EphA7