Role of Betaglycan in gonadal and adrenal tumourigenesis

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/338516

Funding Status
Closed

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Funded Activity Summary

TGF-beta and inhibin are related multifunctional growth factors which regulate a number of important cellular functions, including proliferation, differentiation, and survival. Betaglycan is a cell-surface protein that binds both inhibin and TGF-beta. Betaglycan appears to regulate the binding and availability of the TGF-betas and inhibins to their signaling receptors, and its presence on the cell surface increases the efficiency of TGF-beta and inhibin function. Deletion of the inhibin gene in mice produces tumours in the ovary, testis, and adrenal gland in 100% of the mice. In this current proposal, we will delete the betaglycan gene in the primary target tissues for inhibin (the anterior pituitary and gonads). The hypothesis we are testing is that the loss of a co-receptor for inhibin (i.e. betaglycan) results in a loss of cellular sensitivity to inhibin, thus resulting in altered growth characteristics which predispose the gonads and adrenals to cancer. We will examine these cells in culture and in living animals to determine whether our hypotheses are correct. We will also conduct a series of histological, biochemical, and biological experiments in order determine the underlying causes of any observed growth dysregulation. This work is expected to yield information relevant to the role of betaglycan in inhibin-TGFb-regulated processes in normal and cancerous growth, which may allow future design of therapies for cancer.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $487,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Oncology and Carcinogenesis

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

FSH and LH | adrenal tumours | betaglycan | cachexia | conditional gene knockouts | endocrine tumours | gonadal and adrenal tumourigenesis | inhibins, activins, TGF-betas | reproductive health | sex cord tumours

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