Activin B and Activin C Have Opposing Effects on Prostate Cancer Progression and Cell Growth

SIMPLE SUMMARY: Prostate cancer is one of the leading causes of death in men. Current methods for grading and determining treatment options are not as accurate as they need to be with some men either undergoing unnecessary, life-changing treatment or not being treated and developing late-stage disease. We assessed the effect of proteins called activins on the growth of prostate cell lines and examined their expression in prostate cancer biopsy samples from patients with different grades of tumor. Activin B and activin C were shown to have increased and decreased expression, respectively, in higher grade prostate cancer and to have opposing effects on prostate cell growth and migration. Therefore, these proteins are potential markers for distinguishing aggressive from indolent prostate cancer and may also provide novel targets for prostate cancer treatment. ABSTRACT: Current prognostic and diagnostic tests for prostate cancer are not able to accurately distinguish between aggressive and latent cancer. Members of the transforming growth factor-β (TGFB) family are known to be important in regulating prostate cell growth and some have been shown to be dysregulated in prostate cancer. Therefore, the aims of this study were to examine expression of TGFB family members in primary prostate tumour tissue and the phenotypic effect of activins on prostate cell growth. Tissue cores of prostate adenocarcinoma and normal prostate were immuno-stained and protein expression was compared between samples with different Gleason grades. The effect of exogenous treatment with, or overexpression of, activins on prostate cell line growth and migration was examined. Activin B expression was increased in cores containing higher Gleason patterns and overexpression of activin B inhibited growth of PNT1A cells but increased growth and migration of the metastatic PC3 cells compared to empty vector controls. In contrast, activin C expression decreased in higher Gleason grades and overexpression increased growth of PNT1A cells and decreased growth of PC3 cells. In conclusion, increased activin B and decreased activin C expression is associated with increasing prostate tumor grade and therefore have potential as prognostic markers of aggressive prostate cancer.