TUMORIGENIC BEHAVIOR OF C-HA-RAS ONCOGENE TRANSFECTED CACO-2 CELLS ISASSOCIATED WITH INCREASED PROTEOLYTIC POTENCY

Background. Point mutations within the family of the ras genes are det ected 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 suita ble for gaining more insight into the mechanism of c-Ha-ras induced tu morigenesis. Material and methods: Proliferation, differentiation, and proteolytic capacity of c-Ha-ras oncogene transfected CaCo 2 cells we re studied in vitro. Results: It was found that gelatinolytic capacity and production of urokinase-type plasminogen activator increased, whe reas the production of tissue-type plasminogen activator was similar. Proliferative activity, as measured by the potential doubling time, di d not alter. The expression of the differentiation markers sucrase-iso maltase, mucin, and chromogranin A was not different from that of the parental CaCo 2 cell line, which indicates that an increased tumorigen ic capacity of c-Ha-ras oncogene transfected CaCo 2 cells is not accom panied by loss of differentiation. Conclusion: These data demonstrate that the highly increased tumorigenic capacity of c-Ha-ras oncogene-tr ansfected CaCo 2 cells is associated with an enchanced proteolytic cap acity.