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Publication : Oncogenic activation of Neu/ErbB-2 in a transgenic mouse model for breast cancer.

First Author  Muller WJ Year  1998
Journal  Biochem Soc Symp Volume  63
Pages  149-57 PubMed ID  9513719
Mgi Jnum  J:72137 Mgi Id  MGI:2151771
Citation  Muller WJ, et al. (1998) Oncogenic activation of Neu/ErbB-2 in a transgenic mouse model for breast cancer. Biochem Soc Symp 63:149-57
abstractText  Recent evidence has suggested that amplification and overexpression of erbB-2/neu is an important determinant in the initiation and progression of human breast cancer. Consistent with this assertion is the observation that transgenic mice that overexpress the neu proto-oncogene heritably develop mammary adenocarcinomas. More recently, we have demonstrated that activation of neu in many of these tumours occurs as a result of somatic mutations located within the transgene itself. Indeed, careful examination of the altered neu transcripts revealed the presence of in-frame deletions that encode aberrant Neu receptors lacking 5-12 amino acids within the extracellular domain, located adjacent to the transmembrane domain. Interestingly, the majority of the deletions analysed affect one of several conserved cysteine residues present within this region. Moreover, introduction of these activating mutations into the wild-type neu cDNA results in its oncogenic conversion. These observations suggest that this cysteine-rich region plays an important role in regulating the catalytic activity of Neu.
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