Biology and pathology of GRP precursors [ 2007 - 2009 ]

Research Grant

Researchers: Prof Arthur Shulkes (Principal investigator) ,  Dr Oneel Patel ,  Prof Graham Baldwin

Brief description Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce their own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to deterrmine the potential roles of a growth factor termed bombesin. This peptide, now known as GRP in mammalian systems, is an established growth factor in certain lung cancers but little is known about its role in tumours of the large bowel. This project is based on our novel observation that the precursor of GRP (proGRP) previously thought to be inactive is in fact biologically active in stimulating the growth of colorectal carcinoma cells. We will determine which parts of the GRP precursor (proGRP) are bioactive, and test the effects of the bioactive regions on growth and cancer spread using a variety of colorectal cancer cell lines. We will also investigate the effects of the bioactive regions of proGRP on the development of colorectal cancer in three animal models, which represent different stages of the progression to invasive cancer. We will then compare the intracellular pathways by which proGRP and GRP communicate with the cell nucleus, and investigate the structure of the cell-surface receptor that binds the proGRP. Finally we will determine the types and amounts of proGRP derived peptides produced by CRC cell lines and by tumours obtained from patients with colorectal cancer. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as proGRP receptor antagonists and radioactive proGRP analogues for radiotherapy.

Funding Amount $AUD 496,446.74

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant