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

Division of Hematology/Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, USA

Key Words. HER-2/neu • erbB receptors • Signal transduction • Breast cancer • Ovarian cancer • Heregulin • Epidermal growth factor

Dr. Dennis J. Slamon, University of California at Los Angeles, Department of Medicine, Division of Hematology/Oncology, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.

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-. 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.

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