Using transgenic mice we show that the in vivo growth-inducing properties are associated with the extracellular portion of the molecule. The programmed cell death-inducing properties are associated with the cytoplasmic region. Given the relative importance of the EGF receptor pathway in human mammary oncogenesis, we were anxious to establish a mouse model system that more closely resembles the human situation in which the ErbB-2 gene is amplified and overexpressed. We created a transgenic mouse using a construct consisting of the neu transgene following the neu promoter. In analyzing this model we note that the subtle overexpression of this gene in the mammary gland of the nullparous female induces ductal enlargement, precosious lobular development, alveolar hyperplasia, and formation of multiple malignant foci.
Multiparous females develop palpable mammary gland tumors late in life.
This model should play an important role in development and testing of therapeutic and preventive measures associated with breast carcinoma. E-mail the Webmaster.