Transforming Genes of Neoplasms

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This chapter discusses the specificity of transforming genes activated in mammary carcinomas and lymphoid neoplasms. It also discusses the relationship between the transforming genes of human bladder and lung carcinomas and ras genes of Harvey and Kirsten sarcoma viruses. The transforming genes activated in a human mammary carcinoma cell line, a chemically induced mouse mammary carcinoma, and five virus-induced mouse mammary carcinomas are analyzed in the chapter by comparing the susceptibility of the transforming activities of these tumor DNAs to digestion with seven different restriction endonucleases. In this study, transforming activities of all seven mammary carcinoma DNAs were inactivated by digestion with endodeoxyribonucleases PvuII and Sac1 but not by BamHI, EcoRI, HindIII, KpnI, or XhoI. Because the probability of seven different genes yielding this pattern of susceptibility to cleavage by these restriction endonucleases is less than 10-10, the results indicate that the same or closely related transforming genes were activated in a human mammary carcinoma and in six independent mouse mammary carcinomas induced by either viral or chemical carcinogens. The chapter also discusses the molecular cloning and analysis of a transforming gene activated in chicken B-cell lymphomas. A biologically active transforming gene has been isolated from NIH cells transformed by chicken B-cell lymphoma DNA. DNA of these transformed NIH cells was cloned as a random library in A Charon 30, and this phage library was screened by sib-selection using transfection as an assay to identify recombinant phage containing an active transforming sequence.

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