The contribution of inhibins and activins to malignant prostate disease

The normal human prostate expresses inhibin and activin subunits. In prosta te cancer, the inhibin alpha subunit gene is down regulated and this is ass ociated with loss of heterozygosity (LOH) at the gene locus and methylation of the promoter. These data support the hypothesis that the inhibin alpha subunit is tumor suppressive in the prostate. The pluripotent effects of ac tivins and the similarities to transforming growth factor beta (TFG beta) s uggest a role for activins in progression to malignancy, whereby, the norma l growth inhibitory action of activin A observed on benign cells is lost wi th the acquisition of activin resistance in prostate cancer cells. The mech anisms of rendering tumor cells resistant to activin A may include: alterat ion in activin binding protein (follistatin) synthesis and/or dimerisation with activin beta (C) to form novel activin dimers. The contribution of the activin signalling cascade to malignancy requires further evaluation to id entify the synergies and differences to other members of the TGF beta super family, (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.