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

Inhibin is a member of the TGF-beta superfamily of growth and differentiation factors and a tumor suppressor. Consistent with the tumor suppressive function of the inhibin alpha 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 alpha subunit immunoreactivity. Paradoxically, an expanded study to evaluate the prognostic significance of inhibin alpha 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 alpha 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.