Abstract
Expression of the activated neu oncogene in transgenic mice has been associated 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 transgenic mice carrying the activated neu oncogene under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were produced. Activated neu transgene expression, as measured by in situ hybridization and ribonuclease protection assays, resulted in rapid conversion of the normal mammary epithelium to malignant phenotype in three independent strains of mice. Expression of the transgene in male mice led to epithelial hyperplasia of the epididymis and male infertility but not malignancy. These results indicate that tissue context is an important parameter in malignant progression and that expression of appropriate levels of activated neu is sufficient for rapid production of mammary tumors in transgenic mice.
Highlights
Expression of the activated neu oncogene in transgenic mice has been associated with both the synchronous and the stochastic transformation of the mammary epithelium
Generation of MMTV/Activated neu Transgenic Mice and Tissue Specificity of Expression—To target expression of the activated neu oncogene to the mammary epithelium, two different MMTV/activated neu fusion genes were microinjected into one cell mouse embryo
Truncation of these long terminal repeats (LTR) sequences is known to affect the temporal pattern of expression of the transgene during mammary gland development [16]
Summary
Expression of the activated neu oncogene in transgenic mice has been associated with both the synchronous (single-step) and the stochastic (multistep) transformation of the mammary epithelium. The human homologue of neu oncogene (c-erbB-2) was shown to be amplified and expressed in many human primary breast cancers [3,4,5], and its amplification inversely correlated with patient survival [6, 7]. Given the limitations of these studies, a number of laboratories have turned to the transgenic mouse to directly assess the oncogenic potential of neu in the mammary epithelium. This was accomplished by linking the mouse mam-.
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