Neuregulin-1 (NRG1) in colorectal cancer

Mirza, Nazzia Nosheen (2009). Neuregulin-1 (NRG1) in colorectal cancer. University of Birmingham. Ph.D.

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Abstract

Previous studies identified a distinct region of interstital deletion at c8p12 locus in colorectal cancer. Deletions at c8p12 were more frequent in early than advanced colorectal tumours. Further studies defined more closely this interstitial deletion, implicating a cluster of genes close to marker D85259 in early colorectal tumours. Although interstitial deletions normally correspond to tumour suppressor genes, the above findings suggest that this region contains genes with tumour suppressive and oncogenic effects. We investigated NRG1, one of the genes in this region in colorectal tumourigenesis.

To determine the expression profile of NRG1 , multiple approaches were utilised. Results from these studies identified deletion (loss of one allele) of \(NRG1\) in early colorectal tumours. Increased expression of NRG1 protein was identified in advanced tumours compared to early colorectal tumours and adenomas. A significant correlation between NRG1 protein expression and erb82 protein overexpression was identified. Although the range of NRG1 isoforms expressed was qualitatively similar throughout tumour progression, semi-quantitative real-time RT -PCR, showed overall decreased expression in early tumours compared with normal tissue. In advanced cancers, the results were more heterogeneous, but no consistent pattern emerged between the cases investigated.

Although these studies did not demonstrate any functional relationship, the data strengthens the candidacy of a role for NRG1 in colorectal tumour progression.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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