Physiological significance of cellular translocation of the intestine-specific homeodomain protein Cdx2

Funded Activity Summary

Ulcerative colitis and Crohn's disease are debilitating inflammatory diseases of the bowel. Conservative estimates (Australian Crohn's and Colitis Association) suggest that at least 23,000 Australians are affected (>1 in 1000). Ten years after onset, there is an estimated risk of 0.5-1.0% per year of pancolitis patients developing full-blown bowel cancer. Current therapies for colon cancer are not very effective and the median survival for patients with metastatic disease is poor at 7-12 months. It is therefore important to increase our understanding of the biology underlying these inflammatory conditions so that more effective treatments may be developed and fewer patients proceed to the cancerous stage. We have recently demonstrated a novel interaction between two proteins that may be relevant to intestinal inflammation. Surprisingly, the two proteins would not normally be expected to coincide with each other because of their different localisations within cells and tissues. The first protein, Cdx2, is only synthesised by intestinal lining cells and normally resides in the nucleus where it activates genes that play a role in the highly specialised absorptive functions of the intestine. The other protein, acrogranin-granulin, is more widely distributed in the body and is generally transported out of cells shortly after it has been made. It has been shown to interact with receptors on epithelial cells and blood cells and promotes their growth. In this proposal we will be investigating whether the complex formed between Cdx2 and granulin is important for normal physiology. Moreover since elevated levels of granulin are associated with inflammation, we aim to determine whether the Cdx2-granulin complex is formed during the active phase of ulcerative colitis and Crohn's disease. Specifically, we will test the hypothesis that the Cdx2-granulin complex plays an important role in repairing the damage caused to the lining of the intestine during inflammation.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $196,527.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Protein Targeting And Signal Transduction

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Cdx2 | Colorectal cancer | Crohn's disease | Epithelial cells | Granulins/epithelins | Homeodomain transcription factors | Inflammatory bowel disease | Intestinal biology | Ulcerative colitis

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