HER‐2/neu Signal Transduction in Human Breast and Ovarian Cancer

The HER‐2/neu proto‐oncogene encodes a 185 kDa transmembrane receptor tyrosine kinase with significant sequence homology to other members of the class I receptor tyrosine kinase family. The HER‐2/neu gene is amplified and/or overexpressed in 25%‐30% of human breast and ovarian cancers, and overexpression of the receptor is associated with poor prognosis. Tyrosine phosphorylation and activation of the HER‐2 receptor lead to activation of specific signal transduction pathways in breast and ovarian cancer cells, including the ras/MAP kinase cascade, phosphatidylinositol 3‐kinase, and phospholipase C‐γ. HER‐2/neu signal transduction pathways ultimately converge on the cell nucleus, where the expression of diverse genes is induced after activation of the receptor. A more complete understanding of HER‐2/neu signal transduction pathways may allow the development of specific therapeutics for the treatment of those human breast and ovarian cancers containing this alteration.