期刊
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
卷 6, 期 4, 页码 393-406出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1023/A:1014730829872
关键词
HER2/neu/c-erbB-2; invasion; metastasis; drug resistance; angiogenesis; signaling pathways
Gene amplification and/or overexpression of the c-erbB-2/HER2/neu tyrosine kinase are linked with poor prognosis in breast cancer. This is manifest in shorter disease-free intervals, increased risk of metastasis. and resistance to many types of therapy. The molecular mechanisms and signaling circuitry underlying these phenomena are now being elucidated. c-erbB-2, although having no known soluble ligand, is transactivated by heterodimerization with other family members (EGFR. c-erbB-3. c-erbB-4). Receptor activation potentiates tumor cell motility, protease secretion and invasion, and also modulates cell cycle checkpoint function, DNA repair, and apoptotic responses. Since it is expressed at low levels in normal adult tissues, c-erbB-2 is an ideal target for therapy. There is reason for optimism that agents targeting c-erbB-2 signaling will have profound and selective effects in breast cancer, either as single agents or more likely in combination with other therapeutic agents, to enhance their potency.
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