Regulation of Gene Expression in Cancer: The Relationship of STAT1, MMP-1 and MMP-3
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Malignant melanoma and colorectal cancer are two diseases of considerable importance to the populations of developed countries as leading causes of cancer related death. Malignant melanoma is also important due to its high and rapidly increasing incidence. Due to their respective geographical locations, Australia and New Zealand share the highest rates of malignant melanoma in the world. Colorectal cancer is the second most common cause of cancer related death in Australia after lung cancer. Interferon (IFN)-α is currently one of the preferred agents for adjuvant therapy of advanced stage melanoma due to its ability to arrest growth and promote the death of tumour cells with some degree of selectivity. However despite this, response rates to this drug remain unacceptably low, in the range of 15 to 20%. Deficiencies in the expression of the STAT1 transcription factor have previously been shown to correlate with the resistance of melanoma cells to the type I IFNs (IFN-α and IFN-β). Given the importance of STAT1 and other components of the ISGF3 cell signaling complex for responses of melanoma cells to type I IFN, potential causes for the loss of STAT1 expression in melanoma cells have been investigated. Despite the presence of a strong CpG island region in the promoter of the STAT1 gene, methylation of this island did not appear to be the cause for the loss of STAT1 expression in melanoma cells.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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