Multiple Steps in the in vitro Immortalisation and Neoplastic Conversion of Human Colonic Epithelial Cells

Abstract

The development of colorectal cancer is an excellent example of the complex multistep nature of carcinogenesis. A clear premalignant stage has been recognised, the adenoma, from which most colorectal cancers develop. There have been important recent developments in the cellular and molecular biology of colorectal cancer, in particular the mapping of the Familial adenomatous polyposis (FAP) gene to chromosome 5 (1,2) and the realization that both activation of dominantly acting oncogenes (ras gene in particular) and loss of tumour suppressor genes are involved in colorectal carcinogenesis. Common genetic alterations that occur during colorectal carcinogenesis include deletions on chromosomes 1, 5, 17, 18 and 22 (reviewed in 3,4). To study colorectal carcinogenesis we have previously isolated epithelial cell lines from sporadic and FAP adenomas (5, 6) with the following objectives: (i) To develop markers to distinguish the different premalignant adenoma stages (ii) To establish an in vitro model for tumour progression by transforming premalignant human colonic adenoma cells to the malignant phenotype. This work is reviewed in this paper.