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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 alpha-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-betaC 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-betaC 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-betaC modulated the development of reproductive tumors but had no effect on adrenal tumorigenesis. Our data reinforces the importance of activin-betaC in reproductive biology and suggest that activin-betaC is a tumor modulator with gonadal specificity.
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