ACTIVATED NEU INDUCES RAPID TUMOR PROGRESSION

Expression of the activated neu oncogene in transgenic mice has been a ssociated with both the synchronous (single-step) and the stochastic ( multistep) transformation of the mammary epithelium, To determine the basis for these conflicting observations, additional strains of transg enic mice carrying the activated neu oncogene under the transcriptiona l control of the mouse mammary tumor virus promoter/enhancer were prod uced. Activated neu transgene expression, as measured by in situ hybri dization and ribonuclease protection assays, resulted in rapid convers ion of the normal mammary epithelium to malignant phenotype in three i ndependent strains of mice. Expression of the transgene in male mice l ed to epithelial hyperplasia of the epididymis and male infertility bu t not malignancy. These results indicate that tissue context is an imp ortant parameter in malignant progression and that expression of appro priate levels of activated neu is sufficient for rapid production of m ammary tumors in transgenic mice.