Receptor tyrosine kinase (RTK) activity is essential for erbB2 (HER2/neu) promotion of breast carcinogenesismetastasis and therapeutic resistance.ErbB2 kinase can be activated by dimerization with another erbB receptor,most of which bind ligands.Of these, the erbB2/erbB3 heterodimer is the most potent oncogenic comPlex.Using tumor-derived cell lines from those MMTV-neu transgenic mice, we first indicated that tumor cell growth promotion,activation of erbB2/neu tyrosine kinase and its downstream signaling Akt and MAPK by E2 were observed exclusively in mammary tumor cells with co-expression oferbB2/neu and erbB3.Further, this activation oferbB2/neu signaling could be abrogated by downregulation of erbB3 through a spceific siRNA, suggesting that the hetero-dimerization complex erbB2/erbB3 is requisite for estrogenic promotion of erbB2/neu tyrosine kinase activation and downstream signaling in mammary tumorigenesis.