Expression Of Bfl-1 And Its Anti-apoptosis Function In Prostate Adenocarcinoma

Background: Prostate adenocarcinoma is one of the major malignancies of the genitourinary system. In American, it is the most common malignancy and the second leading cause of cancer mortality in the male. In China, the incidence and detection rate of prostate adenocarcinoma are increasing. Almost all early stage prostate adenocarcinomas require androgen for growth, but most ultimately progress to an androgen-independent status. The hormonal refractory prostate cancer (HRPC) is highly resistant to various therapeutics including endocrine therapy, chemotherapy and radiotherapy, indicating serious deregulation of apoptosis in HRPC. We have previously shown that expression of Bfl-1 in androgen-dependent and androgen-independent prostate cancer cell lines as well as normal prostate glandular epithelium are different. However, the expression of Bfl-1 in prostate cancer and its function are still unknown. The present study aims to: (1) determine the expression of Bfl-1 mRNA in prostate cancer cell lines and tissues; (2) to explore the functions of Bfl-1 in prostate adenocarcinoma.Materials and methods: (1) RT-PCR, real-time quantitative PCR and in situ hybridization were used to detect the expression of Bfl-1 mRNA in prostate cancer cell lines. (2) The expression of Bfl-1 mRNA in 67 prostate adenocarcinoma and 25 BPH tissue samples were examined by using in situ hybridization (ISH). (3) Expression of Bfl-1 in prostate cancer cell lines was targeted by antisense technology, and the effect of which on tumor cell viability and on the expression of several proliferation and apoptosis regulatory molecules were examined.Result: Expression of Bfl-1 mRNA in prostate cancer cell lines and normal prostate glandular epithelium were examined by RT-PCR, real-time quantitative PCR and in situ hybridization. The results displayed that: Bfl-1 mRNA was overexpressed in the androgen-independent prostate cancer cell lines (DU145 and PC-3), but barely detectable in androgen-independent prostate cancer cell line LNCaP and normal prostate cells.Bfl-1 mRNA expression rate in 67 cases of prostate adenocarcinoma tissues was 58.2% (39/67), but was only 32% (8/25) in 25 cases of BPH tissues. The difference of Bfl-1 expression between benign and malignant prostate tissues was statistically significant (p=0.025).Antisense oligonucleotides (ASONs) targeting Bfl-1 inhibited androgen-independent prostate cancer cell growth. Expression knockdown of Bfl-1 in DU145 upregulated apoptosis inducing factor (AIF) expression.Conclusion: (1) Bfl-1 mRNA is overexpressed in the androgen-independent prostate cancer cell lines (DU145 and PC-3), but is barely detectable in androgen-independent prostate cancer cell line LNCaP, suggesting that Bfl-1 may be involved in androgen resistance of prostate cancer. (2) Bfl-1 mRNA is overexpressed in prostate adenocarcinoma tissues, but its expression level in benign prostate hyperplasia is much lower. (3) Targeting Bfl-1 could suppress androgen-independent prostate cancer cell growth.