Androutsopoulos G, Michail G, Adonakis G, Decavalas G (2015) Molecular Mechanisms, Expression and Clinical Role of Erbb Receptors in Endometrial Cancer. Int J Clin Ther Diagn. S1:006 28-32 28 http://scidoc.org/IJCTD.php International Journal of Clinical Therapeutics and Diagnosis (IJCTD) ISSN 2332-2926 Molecular Mechanisms, Expression and Clinical Role of ErbB Receptors in Endometrial Cancer Review Article Androutsopoulos G 1* , Michail G 2 , Adonakis G 3 , Decavalas G 4 1 Assistant Professor, Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion, Greece. 2 Lecturer of Obstetrics & Gynecology, Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion, Greece. 3 Assoc. Professor of Obstetrics & Gynecology, Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion, Greece. 4 Professor, Head of the Department of Obstetrics & Gynecology, Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion, Greece. *Corresponding Author: Georgios Androutsopoulos MD, Assistant Professor, Department of Obstetrics & Gynecology, Univer- sity of Patras, Medical School, Rion 26504, Greece. Tel: +306974088092 E-mail: androutsopoulos@upatras.gr, androutsopoulosgeorgios@hotmail.com Received: December 24, 2014 Accepted: April 27, 2015 Published: April 29, 2015 Citation: Androutsopoulos G, Michail G, Adonakis G, Decavalas G (2015) Molecular Mechanisms, Expression and Clinical Role of Erbb Re- ceptors in Endometrial Cancer. Int J Clin Ther Diagn. S1:006 28-32. Copyright: Androutsopoulos G © 2015. This is an open-access article distributed under the terms of the Creative Commons Attribution Li- cense, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Introduction The epidermal growth factor system (EGF system) is present in various human organs. It has an important role in cell prolif- eration, differentiation and apoptosis during embryogenesis and postnatal development [1, 2]. Dysregulation of the EGF system signaling network is involved in cancer, diabetes, autoimmune, infammatory, cardiovascular and nervous system disorders [1, 3]. Especially in cancer, the EGF system signaling network becomes hyperactivated with a variety of mechanisms (ligand overproduc- tion, receptor overproduction, constitutive receptor activation) [3, 4]. Furthermore, the EGF system in cancer contributes in prolifera- tion, transformation, angiogenesis, migration and invasion [5]. Recent years the receptors of the EGF system, are potential tar- gets in cancer treatment [6, 7]. Molecular Biology of ErbB Receptors The EGF system has 4 receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands [1, 4, 5]. ErbB receptors are trans-membrane glycoproteins and belong to the superfamily of Receptor Tyrosine Kinases (RTKs) [1, 5]. They have an extracellular region with two ligand-binding domains, an extracellular juxtamembrane region, a hydrophobic transmem- brane domain and an intracellular domain with tyrosine kinase activity [4, 8]. They catalyze the transfer of the γ phosphate of ATP to the hydroxyl groups of tyrosines in target proteins [9]. The extracellular region of EGFR, ErbB-3 and ErbB-4 has 2 dis- Special Issue on "Endometrial Cancer: Pathogenesis, Diagnosis And Treatment" Abstract The epidermal growth factor system (EGF System) is present in various human organs. It has 4 receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands. Especially in cancer, the epidermal growth factor system signaling network be- comes hyperactivated with a variety of mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). ErbB receptors are trans-membrane glycoproteins. Dimerization of ErbB receptors leads to intracellular kinase activation and initiates intracellular signaling via several pathways. Due to the inactive status of postmenopausal endometrium, we expect to fnd signifcantly higher expression of the 4 ErbB receptors in endometrial cancer tissue. In unselected endometrial cancer patients, there is EGFR expression in 43-67% of cases. EGFR overexpression in patients with Type I endometrial cancer, did not affect disease progression. However EGFR overexpression in patients with Type II endometrial cancer, associated with high grade disease and adverse clinical outcome. In unselected endometrial cancer patients, ErbB-2 amplifcation/overexpression represents a rare event. ΕrbB-2 overex- pression especially in patients with Type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival. Recent years ErbB receptors (especially EGFR and ΕrbB-2) have a particular importance, as they are potential targets in endometrial cancer treatment.