| First Author | Gold E | Year | 2013 |
| Journal | J Pathol | Volume | 229 |
| Issue | 4 | Pages | 599-607 |
| PubMed ID | 23180294 | Mgi Jnum | J:302259 |
| Mgi Id | MGI:6507971 | Doi | 10.1002/path.4142 |
| Citation | Gold E, et al. (2013) Activin-beta(c) reduces reproductive tumour progression and abolishes cancer-associated cachexia in inhibin-deficient mice. J Pathol 229(4):599-607 |
| abstractText | Activins are involved in the regulation of a diverse range of physiological processes including development, reproduction, and fertility, and have been implicated in the progression of cancers. Bioactivity is regulated by the inhibin alpha-subunit and by an activin-binding protein, follistatin. The activin-beta(C) subunit was not considered functionally significant in this regard due to an absence of phenotype in knockout mice. However, activin-beta(C) forms heterodimers with activin-beta(A) and activin-C antagonizes activin-A in vitro. Thus, it is proposed that overexpression, rather than loss of activin-beta(C) , regulates activin-A bioactivity. In order to prove biological efficacy, inhibin alpha-subunit knockout mice (alpha-KO) were crossed with mice overexpressing activin-beta(C) (ActC++). Deletion of inhibin leads to Sertoli and granulosa cell tumours, increased activin-A, and cancer-associated cachexia. Therefore, cachexia and reproductive tumour development should be modulated in alpha-KO/ActC++ mice, where excessive activin-A is the underlying cause. Accordingly, a reduction in activin-A, no significant weight loss, and reduced incidence of reproductive tumours were evident in alpha-KO/ActC++ mice. Overexpression of activin-beta(C) antagonized the activin signalling cascade; thus, the tumourigenic effects of activin-A were abrogated. This study provides proof of the biological relevance of activin-beta(C) . Being a regulator of activin-A, it is able to abolish cachexia and modulate reproductive tumour development in alpha-KO mice. |
