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Bioactivity is regulated by the inhibin \u03b1\u2010subunit and by an activin\u2010binding protein, follistatin. The activin\u2010<jats:styled-content style=\"fixed-case\">\u03b2<jats:sub>C<\/jats:sub><\/jats:styled-content> subunit was not considered functionally significant in this regard due to an absence of phenotype in knockout mice. However, activin\u2010<jats:styled-content style=\"fixed-case\">\u03b2<jats:sub>C<\/jats:sub><\/jats:styled-content> forms heterodimers with activin\u2010<jats:styled-content style=\"fixed-case\">\u03b2<jats:sub>A<\/jats:sub><\/jats:styled-content> and activin\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> antagonizes activin\u2010A <jats:italic>in vitro<\/jats:italic>. Thus, it is proposed that overexpression, rather than loss of activin\u2010\u03b2<jats:sub>C<\/jats:sub>, regulates activin\u2010A bioactivity. In order to prove biological efficacy, inhibin \u03b1\u2010subunit knockout mice (\u03b1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) were crossed with mice overexpressing activin\u2010<jats:styled-content style=\"fixed-case\">\u03b2<jats:sub>C<\/jats:sub><\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">ActC<\/jats:styled-content>++). Deletion of inhibin leads to Sertoli and granulosa cell tumours, increased activin\u2010A, and cancer\u2010associated cachexia. Therefore, cachexia and reproductive tumour development should be modulated in \u03b1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ActC<\/jats:styled-content>++ mice, where excessive activin\u2010A is the underlying cause. Accordingly, a reduction in activin\u2010A, no significant weight loss, and reduced incidence of reproductive tumours were evident in \u03b1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ActC<\/jats:styled-content>++ mice. Overexpression of activin\u2010<jats:styled-content style=\"fixed-case\">\u03b2<jats:sub>C<\/jats:sub><\/jats:styled-content> antagonized the activin signalling cascade; thus, the tumourigenic effects of activin\u2010A were abrogated. This study provides proof of the biological relevance of activin\u2010<jats:styled-content style=\"fixed-case\">\u03b2<jats:sub>C<\/jats:sub><\/jats:styled-content>. Being a regulator of activin\u2010A, it is able to abolish cachexia and modulate reproductive tumour development in \u03b1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4142","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T04:25:15Z","timestamp":1353903915000},"page":"599-607","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Activin\u2010\u03b2<sub>c<\/sub> reduces reproductive tumour progression and abolishes cancer\u2010associated cachexia in inhibin\u2010deficient mice"],"prefix":"10.1002","volume":"229","author":[{"given":"Elspeth","family":"Gold","sequence":"first","affiliation":[{"name":"Department of Anatomy University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco 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