The role of inhibins and activins in prostate cancer pathogenesis.

Abstract

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 β (TGFβ) 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 TGFβ 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 TGFβ 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.

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

“…Furthermore, mean Activin A serum concentrations were significantly more elevated in PC patients than in BC patients. This latter phenomenon further indicate, as reported in other studies, that Activin A may be actively involved in the modulation of the osteoblastic activity which, in the case of prostate cancer, is predominant and may account for osteoblastic reactions induced by tumor cells [8,12,23,31,32]. In addition, our results have highlighted that, in PC patients Activin A levels significantly correlated with PSA serum concentrations.…”

“…Several studies suggest that Activin A may have a role in tumor progression [2,3,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The specific [2][3][4].…”

“…The biological effects of Activin A, are mediated through two transmembrane serine/threonine receptor kinases namely, ActRI and ActRII and may be inhibited by a number of Activin binding proteins [1,2,9]. Interestingly, a consistent number of experimental and clinical observations have reported that many human cancers present altered expression levels of Activin A and/or altered levels of its receptors and/or that of its specific inhibitors and that these alterations may be associated with a more malignant tumor phenotype [3,4,[10][11][12][13][14][15][16][17][18][19][20]. Furthermore, recent findings have shown that, Activin A may play an active role in the modulation of osteoblastic activity and in osteoclast differentiation during bone remodeling processes associated to a number of physiological or pathological conditions [1, 5-8, 10, 21, 22].…”

Integrated Analysis Reveals Critical Genomic Regions in Prostate Tumor Microenvironment Associated with Clinicopathologic Phenotypes

“…Furthermore, the relevance to innate immunity lends credence to early hypotheses of metabiomic relationships in initiating various neoplasias (35,37), including that of the prostate. Of note, the activin/TGF-b signaling subnetwork has already been acknowledged to be important in prostate carcinogenesis (38). We have shown that D12S297 harbors the human activin receptor, ACVR1B, which has been described as having somatic mutations and deletions in at least 4 other types of cancers, and which is expressed in prostate epithelium (39).…”

Developing New Small Molecular Drugs for Prostate Cancer Therapy

“…There are several currently known mechanisms for the prostate cancer pathogenesis [7]. Mutation of P53, common in prostate cancer, influenced its downstream effectors, which have been proved mediating prostate cancer processing and causing aberrant nuclear protein accumulation [8][9][10].…”