Gene expression changes induced upon Beta3 integrin expression in human melanoma metastasis

Funding Activity

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Funded Activity Summary

Diagnostic and prognostic markers for metastatic melanoma are essential to better understand the development of this cancer. One of the most effective markers so far found to correlate with invasiveness of tumour cells, and hence lethality of melanoma, is the Beta3 integrin molecule. When this protein is expressed on the surface of early stage melanoma cells, that in themselves are not able to form metastatic tumours, they convey upon the cells the ability to proceed from growing on the surface of the skin (radial growth phase) to allowing them to invade the skin (vertical growth phase). It is not clear how expression of Beta 3 allows this change in growth state to occur and this research program is designed to test if Beta 3 is the direct cause of gene expression changes mediating the metastatic transformation. To provide insight into the genetic changes induced in melanoma cells expressing the Beta3 protein a screen for genes that are either activated or repressed in the presence of Beta3 will be performed. Non-metastatic melanoma cells will be transduced with the Beta 3 gene and a molecular technique applied to these cells that can identify genetic differences which will allow the cloning of differentially expressed genes. The gene fragments that are identified will first provide clues as to what the genes are that maybe switched on or off to allow the tumour to grow beneath the skin. They will also form the basis of a Ometastatic melanoma gene panelO that can be tested for its diagnostic value of tumours. The utility and reproducibility of the gene panel will be confirmed by testing melanoma cell lines and tumour tissue. These experiments should lead to better diagnosis of metastatic melanoma and also possible new avenues to develop therapies for the disease.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $199,413.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Interactions (Incl. Adhesion, Matrix, Cell Wall)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Cell adhesion | Differential gene expression | Integrin | Melanoma | Skin cancer | Tumour invasiveness | Tumour metastasis | Vertical growth phase melanoma