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

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.

Fourth Chromosome Resource Project: a comprehensive resource for genetic analysis in Drosophila that includes humanized stocks

“…Loss-of-function mutations were detected in endometrial and prostate cancer ( Daly et al . 2022 ; Reader et al . 2022 ).…”

Investigating the Role of SNAI1 and ZEB1 Expression in Prostate Cancer Progression and Immune Modulation of the Tumor Microenvironment

“…SFRP2 was identified as a regulator of the TME through its impact on Wnt signaling and tumor angiogenesis [41,42], while THBS4 influenced cancer stem cell-like properties in PCa via the PI3K/Akt pathway [43]. Several other DEGs have been previously associated with higher Gleason scores, including COL1A2 and INHBA (subunit of Activin A) [44,45]. WNT2B is regulated by long non-coding RNAs (lncRNAs) and has been shown to play a role in influencing the EMT in PCa [46], while SFRP4 emerged as a predictor of BCR in PCa, and its expression is also linked to the EMT [47].…”