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- Title
Activin-β<sub>c</sub> reduces reproductive tumour progression and abolishes cancer-associated cachexia in inhibin-deficient mice.
- Authors
Gold, Elspeth; Marino, Francesco Elia; Harrison, Craig; Makanji, Yogeshwar; Risbridger, Gail
- Abstract
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 α-subunit and by an activin-binding protein, follistatin. The activin- βC subunit was not considered functionally significant in this regard due to an absence of phenotype in knockout mice. However, activin- βC forms heterodimers with activin- βA and activin- C antagonizes activin-A in vitro. Thus, it is proposed that overexpression, rather than loss of activin-βC, regulates activin-A bioactivity. In order to prove biological efficacy, inhibin α-subunit knockout mice (α- KO) were crossed with mice overexpressing activin- βC ( 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 α- 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 α- KO/ ActC++ mice. Overexpression of activin- βC antagonized the activin signalling cascade; thus, the tumourigenic effects of activin-A were abrogated. This study provides proof of the biological relevance of activin- βC. Being a regulator of activin-A, it is able to abolish cachexia and modulate reproductive tumour development in α- KO mice.
- Publication
Journal of Pathology, 2013, Vol 229, Issue 4, p599
- ISSN
0022-3417
- Publication type
Article
- DOI
10.1002/path.4142