%0 Journal Article
%T Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications
%A Nida Iqbal
%A Naveed Iqbal
%J Molecular Biology International
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/852748
%X Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Amplification or overexpression of HER2 occurs in approximately 15¨C30% of breast cancers and 10¨C30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers; however, the results have been proved disappointing in other HER2 overexpressing cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2. 1. Introduction The human epidermal growth factor receptor (HER) family of receptors plays a central role in the pathogenesis of several human cancers. They regulate cell growth, survival, and differentiation via multiple signal transduction pathways and participate in cellular proliferation and differentiation. The family is made up of four main members: HER-1, HER-2, HER-3, and HER-4, also called ErbB1, ErbB2, ErbB3, and ErbB4, respectively [1]. All four HER receptors comprise a cysteine-rich extracellular ligand binding site, a transmembrane lipophilic segment, and an intracellular domain with tyrosine kinase catalytic activity [2]. Epidermal growth factor receptor (EGFR, ErbB1, and HER1)¡ªthe first receptor tyrosine kinase, was discovered by Carpenter and coworkers at Vanderbilt University, USA, in 1978 [3]. ErbB stands for its origin in the Erb-b gene responsible for avian erythroblastosis virus. The neu oncogene (also known as HER2, ErbB2, or p185) was discovered by a group of scientists at Massachusetts Institute of Technology, Rockefeller, and Harvard University [4, 5]. The HER2 receptor is a 1255 amino acid, 185£¿kD transmembrane glycoprotein located at the long arm of human chromosome 17 (17q12) [6]. HER2 is expressed in many tissues and its major role in these tissues is to facilitate excessive/uncontrolled cell growth and tumorigenesis [7¨C9]. 2. Function The HER receptors exist as monomers on the cell surface. Upon ligands binding to their extracellular domains, HER proteins undergo dimerization and transphosphorylation of
%U http://www.hindawi.com/journals/mbi/2014/852748/