The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis
Open Access
- 30 April 2007
- journal article
- review article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 26 (45), 6469-6487
- https://doi.org/10.1038/sj.onc.1210477
Abstract
The year 2007 marks exactly two decades since Human Epidermal Growth Factor Receptor-2 (HER2) was functionally implicated in the pathogenesis of human breast cancer. This finding established the HER2 oncogene hypothesis for the development of some human cancers. The subsequent two decades have brought about an explosion of information about the biology of HER2 and the HER family. An abundance of experimental evidence now solidly supports the HER2 oncogene hypothesis and etiologically links amplification of the HER2 gene locus with human cancer pathogenesis. The molecular mechanisms underlying HER2 tumorigenesis appear to be complex and a unified mechanistic model of HER2-induced transformation has not emerged. Numerous hypotheses implicating diverse transforming pathways have been proposed and are individually supported by experimental models and HER2 may indeed induce cell transformation through multiple mechanisms. Here I review the evidence supporting the oncogenic function of HER2, the mechanisms that are felt to mediate its oncogenic functions, and the evidence that links the experimental evidence with human cancer pathogenesis.Keywords
This publication has 180 references indexed in Scilit:
- Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivityBritish Journal of Cancer, 2006
- Phosphotyrosine interactome of the ErbB‐receptor kinase familyMolecular Systems Biology, 2005
- Structure of the extracellular region of HER2 alone and in complex with the Herceptin FabNature, 2003
- Suppression of Neu-induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin EOncogene, 2002
- NEW EMBO MEMBERS' REVIEW: The ErbB signaling network: receptor heterodimerization in development and cancerThe EMBO Journal, 2000
- Cooperative Signaling between α6β4Integrin and ErbB-2 Receptor Is Required to Promote Phosphatidylinositol 3-Kinase-dependent InvasionOnline Journal of Public Health Informatics, 2000
- Overexpression of ErbB2 impairs ligand-dependent downregulation of epidermal growth factor receptors via a post-transcriptional mechanismJournal of Cellular Biochemistry, 1999
- Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimersThe EMBO Journal, 1998
- ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signalingThe EMBO Journal, 1997
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987