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Suppression of Tumorigenicity in Human Cell Hybrids Derived from Cell Lines Expressing Different Activated ras Oncogenes

Department of Microbiology and Molecular Genetics, University of California, Irvine, California 92717 [M. J. A., E. J. S.]; and the National Cancer Institute, Laboratory of Chemoprevention, Bethesda, Maryland 20892 [A. G. G.]

Four different human tissue-derived cell lines, each previously shown to express either a Ha-, Ki-, or N-ras-activated oncogene, were fused in four different paired combinations. The three combinations that involved the tumor line HT1080 (activated N-ras oncogene) were found to be tumorigenic in nude mice, but to different degrees. However, the fusion of the tumor lines EJ and SW480 (activated Ha-ras and Ki-ras, respectively) resulted in hybrid cells suppressed for tumorigenicity. The EJ x SW480 hybrids were found to harbor and express both of the activated ras oncogenes. The results suggest that tumorigenic suppression can occur in the presence of two transforming oncogenes of the ras family and that tumorigenicity associated with ras oncogene activation involves additional mechanisms that may differ among tumor cells.

¹ To whom requests for reprints should be addressed.

Received 9/ 6/88. Revised 12/ 6/88. Accepted 12/ 9/88.