The role of inhibins and activins in prostate cancer pathogenesis.
Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.
Dowling
C R
CR
Institute of Reproduction and Development, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Risbridger
G P
GP
D028341:Activins; D000818:Animals; D006801:Humans; D007265:Inhibins / Q000737:chemistry / Q000502:physiology*; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000502:physiology; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000502:physiology
D028341:Activins; D007265:Inhibins