Her-2/neu (erbB-2) and the cell cycle

Signaling by the HER-2 proto-oncogene product results in the activation of several biochemical pathways, which in turn modulate the expression and function of cell cycle regulators. These alterations of cell cycle regulatory molecules may be critical for the conception and maintenance of the transformed phenotype conferred by HER-2 gene amplification and overexpression. On the other hand, blockade of HER-2 function with a therapeutic intent will require the reversal of these effects on cell cycle regulatory molecules in order for these interventions to be effective. Data is presented to suggest that the G₁ cyclin DI and the cyclin-dependent kinase inhibitor p27^KIP1 may be involved in subversion of the G₁/S traverse by signaling pathways activated by HER-2 function.