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A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene

Oncogene volume 18, pages 7303–7309 (1999)Cite this article

Abstract

Inhibin, a member of the TGF-β superfamily, is synthesized in the testis by Sertoli cells and exerts an endocrine regulatory function on pituitary hormone synthesis. A distinct local function has been proposed, negatively controlling cellular growth in the testis (tumor suppressor activity). A critical test for the identification of a tumor suppressor is the reversal of transformed growth properties upon re-expression of the gene in tumor-derived cell lines. Sertoli cell-derived tumoral lines were previously established from tumors that develop in elderly transgenic males which express in the testis the large T antigen of polyoma virus. Both the tumors and the cells in culture exhibited reduced levels of the inhibin α subunit mRNA. Stable transfectants were generated, in which this subunit was expressed from a heterologous promoter. All of them exhibited a strict inhibition of growth at confluency. On the other hand, in addition to an aging-related decrease in inhibin synthesis, the α subunit gene was down regulated in vivo in cells expressing the viral protein. The conjunction of these two factors accounts for the age-related occurrence of testicular cancers in the transgenic model, again pointing to inhibin as a potent cell growth regulator in the seminiferous epithelium.

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Acknowledgements

We thank C Boitani for the generous gift of recombinant activin, F Ranc for help in cell culture experiments and L Martin for help in setting up the RNase protection assay. The expert technical assistance of M Cutajar and Y Fantéi is gratefully acknowledged. Recombinant human hormones were kindly provided by the National Hormone and Pituitary Program of the National Institute of Diabetes and Digestive and Kidney Diseases. This work was supported by grants from Association pour la Recherche sur le Cancer (France).

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  1. Unité 470 de l'INSERM, Université de Nice, Nice, 06108, cedex, France

    Pascal Lopez, Frédérique Vidal, Minoo Rassoulzadegan & François Cuzin

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  1. Pascal Lopez
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  2. Frédérique Vidal
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Lopez, P., Vidal, F., Rassoulzadegan, M. et al. A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene. Oncogene 18, 7303–7309 (1999). https://doi.org/10.1038/sj.onc.1203143

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