The contribution of inhibins and activins to malignant prostate disease.
The normal human prostate expresses inhibin and activin subunits. In prostate cancer, the inhibin alpha subunit gene is down regulated and this is associated 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 activins and the similarities to transforming growth factor beta (TFGbeta) suggest a role for activins in progression to malignancy, whereby, the normal growth inhibitory action of activin A observed on benign cells is lost with the acquisition of activin resistance in prostate cancer cells. The mechanisms of rendering tumor cells resistant to activin A may include: alteration 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 identify the synergies and differences to other members of the TGFbeta superfamily.
Risbridger
G P
GP
Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, 3168, Victoria, Australia. gail.risbridger@med.monash.edu.au
Mellor
S L
SL
McPherson
S J
SJ
Schmitt
J F
JF
D028341:Activins / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D007265:Inhibins / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000378:metabolism; D021122:Protein Subunits
D021122:Protein Subunits; D028341:Activins; D007265:Inhibins