Roles of autophagy-related genes Beclin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia

Abstract

Prostate cancer (PCa) is common in Western populations and the second leading cause of cancer-related mortality among males in North America, with an increasing morbidity in China and other Asian countries. The aim of this study was to evaluate the protein expression of autophagy-related genes Beclin-1 and LC3 in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and elucidate their association with p53 and Bcl-2. The total protein of 34 PCa and 50 BPH samples was extracted and the expression of Beclin-1 and LC3 was analyzed by western blotting assay. Subsequently, a total of 96 paraffin-embedded BPH tissue samples was subdivided into 2 groups, one group in which patients had received 5α-reductase inhibitor, due to its effect of androgen ablation, and the control group, in which patients had not received the 5α-reductase inhibitor. The samples were randomly collected and examined using immunohistochemical (IHC) analysis. The western blot analysis demonstrated that Beclin-l and LC3 expression was higher in BPH tissues compared to PCa tissues (P<0.001). There was no statistically significant difference between PCas of different Gleason scores (P>0.05). The result of IHC revealed that Beclin-l and LC3 expression in the group of patients who had received the 5α-reductase inhibitor was significantly higher compared to that in the control group; however, the expression of Bcl-2 and p53 was lower (P<0.05). Beclin-1 expression exhibited a negative correlation with Bcl-2 (r=-0.402, P<0.001), whereas LC3 expression exhibited a positive correlation with Beclin-1 (r=0.345, P=0.001) and a negative correlation with Bcl-2 (r=-0.216, P=0.035). It was suggested that autophagy-related genes Beclin-l and LC3 may be involved in the development and progression of PCa. In addition, the expression of these genes was higher in patients with BPH who had received a 5α-reductase inhibitor, due to androgen reduction. As a result, the induced autophagy may reduce the risk of PCa.

Keywords: autophagy; autophagy-related genes; benign prostatic hyperplasia; prostate cancer.

Figure 1

Verification of the expression of Beclin-1 and LC3 using western blot analysis. Beclin-1 and LC3 expression in benign prostatic hyperplasia (BPH) was found to be higher compared to that in prostate cancer (PCa).

Figure 2

The average relative expression values of Beclin-1 and LC3 in benign prostatic hyperplasia (BPH) were 2.09±0.12 and 1.38±0.04, respectively, which were significantly higher compared to those in prostate cancer (PCa) (0.77±0.06 and 0.84±0.03, respectively; P<0.001). ARE, average relative expression.

Figure 3

Immunohistochemical staining of benign prostatic hyperplasia tissues. The staining is cytoplasmic for (A) Beclin-1, (B) LC3 and (C) Bcl-2 and nuclear for (D) p53 (arrow). Original magnification, ×400.