TY - JOUR
T1 - Reorganization of ErbB family and cell survival signaling after knock-down of ErbB2 in colon cancer cells
AU - Hu, Yi Peter
AU - Venkateswarlu, Srinivas
AU - Sergina, Natalia
AU - Howell, Gillian
AU - St. Clair, Patricia
AU - Humphrey, Lisa E.
AU - Li, Wenhui
AU - Hauser, Jennie
AU - Zborowska, Elizabeth
AU - Willson, James K V
AU - Brattain, Michael G.
PY - 2005/7/22
Y1 - 2005/7/22
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M414238200
DO - 10.1074/jbc.M414238200
M3 - Article
C2 - 15888451
AN - SCOPUS:22844446276
SN - 0021-9258
VL - 280
SP - 27383
EP - 27392
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 29
ER -