The role of IGFBP-3-regulated genes

Summary

This project will investigate the cellular actions of a number of genes that have been identified by microarray experiments and being regulated by the growth-regulatory protein, IGF binding protein-3 (IGFBP-3).

Supervisor(s)

Professor Rob Baxter

Research Location

Kolling Institute of Medical Research

Program Type

Masters/PHD

Synopsis

IGFBP-3 is an important growth-regulatory protein that acts in the circulation, in the extracellular environment, and intrace;lularly. A recent microarray analysis discovered a number of genes expressed by HepG2 hepatoma cells, whose expression changes when IGFBP-3 is downregulated by siRNA. Some of genes that were highly downregulated when we downregulated IGFBP-3 include genes associated with cell migration and apoptosis (functions that we know are affected by IGFBP-3). This project will look for changes in these genes in several breast cancer cell lines to see how they might mediate some of the functions of IGFBP-3. The project may extend to cancer-associated fibroblasts (CAFs) since fibroblasts typically express high levels of IGFBP-3 and are probably regulated by it.  The project would start by downregulating IGFBP-3 using siRNA in several cells lines (we are already experienced with this), and monitoring the expression of about a dozen target genes. Interesting and novel ones would then be followed up functionally e.g. testing for effects on cancer cell migration, apoptosis or survival, cell cycle etc. If this is less productive than anticipated, we coud do a microarray analysis on the breast cell lines to look for new IGFBP-3-regulated genes. This project will shed new light on the mechanisms by which IGFBP-3 reglates its many cellular actions. 

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Keywords

IGF, growth factor, IGFBP-3, growth regulation, Cancer

Opportunity ID

The opportunity ID for this research opportunity is: 721

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