Methylation of Integrin alpha 4 and E-Cadherin Genes in Human Prostate Cancer

• Published in: Pathology oncology research Vol. 21; no. 4; pp. 921 - 927
• Main Authors: Mostafavi-Pour, Z, Kianpour, S, Dehghani, M, Mokarram, P, Torabinejad, S, Monabati, A
• Format: Journal Article
• Language: English
• Published: 01-09-2015
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-015-9917-8

Prostate cancer is the second most common malignancy in men worldwide. Abnormal epigenetic alterations such as DNA methylation and histone modification play an important role in tumor initiation, progression and regulation of cancer-related genes such as integrin alpha 4 and E-cadherin. Expression of these genes was determined by semi-quantitative reverse transcriptase-PCR in prostate cancer cell lines, DU145 and PC3, before and after treatment with 5-aza-2-deoxycytidine and trichostatin A. Laser capture microdissection microscopy was used to obtain exclusively affected epithelial cells from prostate gland biopsies of 30 patients with prostate cancer and 40 with benign prostate hyperplasia. DNA bisulfite modifications followed by methylation-specific PCR were used to evaluate the promoter methylation status of E-cadherin and alpha 4 integrin genes in extracted DNA from patients and aforementioned cell lines. The integrin alpha 4 promoter in DU145 was fully methylated, whereas in PC3 cells, partial methylation was detected. E-cadherin was expressed in both cell lines; trichostatin A and 5-aza-2-deoxycytidine treatment had no effect on E-cadherin expression, however the combined treatment of both drugs or 5-aza-2-deoxycytidine alone increased integrin alpha 4 expression. Integrin alpha 4 and E-cadherin were hypermethylated in 66.6 % and 6.6 % of prostate cancer cases, respectively; no hypermethylation was observed in patients with benign prostate hyperplasia. These results together suggest that aberrant DNA methylation is one of the mechanisms involved in integrin alpha 4 expression and may play an important role in human prostate carcinogenesis. In addition, the higher rate of integrin alpha 4 gene methylation in prostate cancer patients elects it as a potential molecular tumor marker.