Reorganization of ErbB Family and Cell Survival Signaling after Knock-down of ErbB2 in Colon Cancer Cells
| Autor: | Jennie Hauser, Lisa E. Humphrey, Srinivas Venkateswarlu, Elizabeth Zborowska, Wenhui Li, Michael G. Brattain, Gillian M. Howell, James K V Willson, Patricia J. St. Clair, Yi Peter Hu, Natalia Sergina |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
animal structures
Cell Survival Receptor ErbB-2 KDEL Immunoglobulin Variable Region Endoplasmic Reticulum Transfection Biochemistry chemistry.chemical_compound ErbB Cell Line Tumor Humans ERBB3 Epidermal growth factor receptor Phosphorylation skin and connective tissue diseases neoplasms Molecular Biology Epidermal Growth Factor biology Endoplasmic reticulum Tyrosine phosphorylation Oncogene Proteins v-erbB Cell Biology Protein Transport chemistry Colonic Neoplasms Cancer research biology.protein Signal transduction Dimerization Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 280:27383-27392 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m414238200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|