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Causal Role for an Activated N-ras Oncogene in the Induction of Tumorigenicity Acquired by a Human Cell Line¹

Department of Tumor Biology, University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030 [M. A. T.]; Laboratory of Molecular Oncology, NCI-FCRF, Frederick, Maryland 21701 [M. A. T., F. S., D. B.]; and Stehlin Foundation for Cancer Research, Houston, Texas [B. C. G.]

ras oncogenes have been found in approximately 15% of the human tumors analyzed. However, a causal role for these genes in the tumorigenesis of human cells has yet to be shown. Tumorigenic late-passage PA-1 human teratocarcinoma cells (L-PA-1) contain an activated N-ras gene. In this report evidence is presented that nontumorigenic early passage revertant PA-1 cells (E-PA-1) contain only the germ-line protooncogene. Introduction by gene transfer of the activated L-PA-1 oncogene induces E-PA-1 cells to form tumors, suggesting that the activated N-ras oncogene has a causal role in the tumorigenesis of these cells.

¹ This work was supported in part by core grant funds P30-CA-16672 from the National Cancer Institute, Department of Health and Human Services, and by CA-42810 from the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at the University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Department of Tumor Biology, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 11/ 3/86. Revised 2/24/87. Accepted 3/13/87.