title: Activin-βC modulates gonadal, but not adrenal tumorigenesis in the inhibin deficient mice.
abstract: Activins and inhibins are involved in the regulation of several biological processes, including reproduction, development and fertility. Deregulation of the inhibin/activin signaling pathway has been implicated in the progression of reproductive and adrenal cancers. Deletion of the inhibin α-subunit results in up-regulation of the circulating levels of activins and this leads to the development of sex-cord stromal tumors followed by a cancer associated-cachexia in mice. When gonadectomy is performed, development of adrenocortical carcinomas is observed. We previously showed that overexpression of activin-βC modulates the development of sex-cord stromal tumors and reduces cancer-cachexia in the inhibin-deficient mice by antagonizing the activin signaling pathway. The adrenal cortex and gonads share in common a large subset of genes, consistent with their common embryonic lineage. Additionally, it has been shown that adrenocortical carcinomas adopt an altered cellular identity resembling the ovary. Therefore, a study to assess the impact of overexpression of activin-βC on the onset of adrenocortical carcinoma in gonadectomized inhibin-deficient mice was warranted. Within the current study we evaluated markers of apoptosis, proliferation, tumor burden, survival analysis and serum levels of activin-A in gonadectomized mice versus sham operated controls. Results showed that overexpression of activin-βC modulated the development of reproductive tumors but had no effect on adrenal tumorigenesis. Our data reinforces the importance of activin-βC in reproductive biology and suggest that activin-βC is a tumor modulator with gonadal specificity.
authors: Department of Anatomy, University of Otago, Dunedin, New Zealand. Electronic address: francescoelia.marino@otagoanatomy.com.
authors: Francesco Elia
authors: FE
authors: Marino
authors: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria.
authors: Gail
authors: G
authors: Risbridger
authors: Department of Anatomy, University of Otago, Dunedin, New Zealand. Electronic address: Elspeth.Gold@otago.ac.nz.
authors: Elspeth
authors: E
authors: Gold
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D005260:Female; D006066:Gonads / Q000601:surgery; D028322:Inhibin-beta Subunits / Q000172:deficiency* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018309:Neoplasms, Gonadal Tissue / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis
chemical_list: C504187:Inhbc protein, mouse; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits
keywords: Adrenal; Gonadectomy; Inhibin; Ovaries; Testis; Tumor