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肿瘤形成评论综述™
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN 打印: 0893-9675
ISSN 在线: 2162-6448

肿瘤形成评论综述™

DOI: 10.1615/CritRevOncog.v5.i2-3.100
pages 313-329

The c-erbB-2 Protein in Oncogenesis: Molecular Structure to Molecular Epidemiology

Paul W. Brandt-Rauf
Division of Environmental Sciences, Department of Medicine and Comprehensive Cancer Center, Columbia University, 60 Haven Avenue, New York, N.Y. 10032
Matthew R. Pincus
Department of Pathology, SUNY Health Sciences Center, 750 East Adams Street, Syracuse, N.Y. 13210
Walter P. Carney
Oncogene Sciences/ Applied Biotechnology, 80 Rogers Street, Cambridge, MA 01242

ABSTRACT

The c-erbB-2 (HER-2, neu) oncogene has been implicated frequently in many human tumors. This oncogene codes for a 185-kDa protein that functions as a transmembrane growth factor receptor. Overexpression of the normal protein or point mutations in the transmembrane domain of the protein have been shown to have a transforming effect. Molecular structure studies of the transmembrane domain provide a plausible explanation for this transforming effect in both cases and relate this to the process of receptor dimerization in the membrane, degradation of the protein with release of the extracellular domain (ECD) into the extracellular environment, and aberrant signal transduction. The release of the ECD into the extracellular environment provides a potential biomarker for the study of signal transduction at the molecular level in vivo. The ECD can be quantitated immunologically in the serum of individuals with cancers associated with p185 overexpression and in individuals at risk for the development of such cancers and can be used to distinguish these individuals from normal, healthy controls. Identification of such individuals by their serum ECD levels combined with specific chemotherapeutic/ chemoprophylactic interventions could allow for improvement treatment and prevention of c-erbB-2-related cancers.


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