Tumorigenic behaviour of c-Ha-ras oncogene transfected CaCo 2 cells is associated with increased proteolytic potency

Point mutations within the family of the ras genes are detected in approximately 50% of human colorectal adenomas and carcinomas. Therefore, it is generally accepted that the occurrence of ras-point mutations constitute an important step in colorectal carcinogenesis. In addition, many studies have demonstrated that the tumorigenicity of the human colorectal carcinoma cell line, CaCo 2, strongly increases after transfection with the c-Ha-ras oncogene. This cell line is suitable for gaining more insight into the mechanism of c-Ha-ras induced tumorigenesis.

Proliferation, differentiation, and proteolytic capacity of c-Ha-ras oncogene transfected CaCo 2 cells were studied in vitro.

It was found that gelatinolytic capacity and production of urokinasetype plasminogen activator increased, whereas the production of tissue-type plasminogen activator was similar. Proliferative activity, as measured by the potential doubling time, did not alter. The expression of the differentiation markers sucraseiso-maltase, mucin, and chromogranin A was not different from that of the parental CaCo 2 cell line, which indicates that an increased tumorigenic capacity of c Ha-ras oncogene transfected CaCo 2 cells is not accompanied by loss of differentiation.

These data demonstrate that the highly increased tumorigenic capacity of c Ha-ras oncogene-transfected CaCo 2 cells is associated with an enchanced proteolytic capacity.