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HER-2/neu signal transduction in human breast and ovarian cancer
1Division of Hematology/Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095, USA.
Abstract:
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-gamma. 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.
Insights
The HER-2/neu proto-oncogene, often overexpressed in breast and ovarian cancers, activates cell signaling pathways. Understanding these pathways could lead to targeted therapies for HER-2/neu-positive cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The HER-2/neu proto-oncogene encodes a receptor tyrosine kinase involved in cell growth.
- Amplification or overexpression of HER-2/neu occurs in 25%-30% of breast and ovarian cancers.
- HER-2/neu overexpression is linked to a poorer prognosis in these cancers.
Purpose of the Study:
- To elucidate the signal transduction pathways activated by HER-2/neu.
- To explore the downstream effects of HER-2/neu activation in cancer cells.
- To identify potential therapeutic targets based on HER-2/neu signaling.
Main Methods:
- Analysis of HER-2/neu gene amplification and protein expression.
- Investigation of tyrosine phosphorylation and receptor activation.
- Mapping of downstream signal transduction cascades (e.g., ras/MAP kinase, PI3K, PLC-gamma).
Main Results:
- HER-2/neu receptor activation triggers specific intracellular signaling pathways.
- These pathways include the ras/MAP kinase cascade, phosphatidylinositol 3-kinase, and phospholipase C-gamma.
- Activated pathways converge on the nucleus, inducing gene expression.
Conclusions:
- Understanding HER-2/neu signaling is crucial for cancer biology.
- Targeting HER-2/neu pathways offers potential for novel cancer therapeutics.
- Further research into these pathways may improve treatment strategies for HER-2/neu-driven cancers.