ONCOGENIC ACTIVATION OF EGF RECEPTOR AND RELATED GENES

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The mechanisms by which genes normally encoding for growth factor receptors can be "activated" as oncogenes is being studied. A molecular clone of the v-erb gene from the ES4 isolate of avian erythroblastosis virus (AEV) has been constructed into a murine retroviral vector (MuLV) and a virus has been obtained after transfection of this DNA into NIH/3T3 cells and "rescued" with a helper leukemogenic virus. This new murine pseudotype of the v-erb gene is now being used to study how it alters the growth properties and the differentiation program of a number of in vitro systems of murine orgin. Molecular constructions have been engineered into retroviral vectors to test the transforming potential of the recently isolated HER 2 gene (also called neu). The amino truncation of the protein "activates" its transforming ability; a double amino and carboxy truncation does not enhance this latter effect (as suggested in other systems). Virus stocks obtained as described above from this transforming counterpart of the HER 2 gene are now being tested in vivo and in vitro.