Re-evaluation of inhibin α subunit as a tumour suppressor in prostate cancer

Inhibin is a member of the TGF-β superfamily of growth and differentiation factors and a tumor suppressor. Consistent with the tumor suppressive function of the inhibin α subunit in prostate cancer, we reported a loss of gene expression due to DNA hypermethylation and loss of heterozygosity (LOH) as well as down regulation of inhibin α subunit immunoreactivity. Paradoxically, an expanded study to evaluate the prognostic significance of inhibin α subunit expression in men with prostate cancer resulted in a contradictory outcome, whereby an up-regulation of subunit expression was recorded. In seeking a more comprehensive explanation for all data sets, we offer a unifying hypothesis. We propose that the tumor suppressor activities of the inhibin α subunit dominate in non-malignant tissue, but its oncogenic activities emerge during tumorigenesis. An explanation such as this, involving a switch in gene function from being tumor suppressive to pro-oncogenic, may account for the discrepant findings in other types of cancer.