title: Reorganization of ErbB family and cell survival signaling after Knock-down of ErbB2 in colon cancer cells.
abstract: The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Yi Peter
authors.initials: YP
authors.lastname: Hu
authors.forename: Srinivas
authors.initials: S
authors.lastname: Venkateswarlu
authors.forename: Natalia
authors.initials: N
authors.lastname: Sergina
authors.forename: Gillian
authors.initials: G
authors.lastname: Howell
authors.forename: Patricia
authors.initials: P
authors.lastname: St Clair
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Humphrey
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Jennie
authors.initials: J
authors.lastname: Hauser
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zborowska
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Brattain
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology*; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000494:pharmacology; D018739:Oncogene Proteins v-erbB / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D004815:Epidermal Growth Factor; D007135:Immunoglobulin Variable Region; D018739:Oncogene Proteins v-erbB; D018719:Erb-b2 Receptor Tyrosine Kinases