| ErbB2/Neu overexpression is observed in 20--30% of human mammary carcinomas and correlates with poor prognosis. We have demonstrated that four ErbB2/Neu tyrosine autophosphorylation sites (YB, YC, YD and YE) are sufficient to mediate transforming signals in vitro and bind distinct adapter proteins, suggesting that transformation functions through distinct pathways. To study the role of each individual tyrosine autophosphorylation site in mammary tumourigenesis, we derived transgenic mice expressing mutant ErbB2/Neu receptors in the mammary gland. Recently, we showed that YB and YD female transgenic mice developed mammary tumours with differences in tumour latency, morphology, and metastatic potential. To further understand the role of the autophosphorylation sites, I characterized the YC and YE transgenic mouse models and showed that although, they exhibit similar phenotypes, they also differ in their latency, morphology and metastatic rate compared to the YB and YD transgenic mouse models. This suggests that recruitment of specific adaptor proteins has distinct biological effects on ErbB2/Neu-mediated mammary tumourigenesis. |
