Dysregulation of cellular signaling by HER2/neu in breast cancer.
Human epidermal growth factor receptor-2 (HER2/neu; erbB2) belongs to a family of four transmembrane receptor tyrosine kinases involved in signal transduction pathways that regulate cell growth and proliferation. Amplification or overexpression of HER2/neu occurs in about 30% of human breast and ovarian cancers and is associated with a poor clinical outcome, including short survival time and short time to relapse. Recent advances in our understanding of HER2/neu signaling pathways have greatly increased our knowledge of breast cancer tumorigenesis and have provided new targets for treating breast and ovarian tumors that overexpress HER2/neu. This review will focus on the signaling network mediated by HER2/neu in breast cancer and discuss our understanding of these pathways, which seem to be particularly important in mediating cell survival and growth under a wide variety of circumstances in breast cancer.
Zhou
Binhua P
BP
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hung
Mien-Chie
MC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D003598:Cytoskeletal Proteins; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D016328:NF-kappa B; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C495270:CTNNB1 protein, human; C497206:MDM2 protein, human