TY - JOUR
T1 - Growth factor regulation of the molecular chaperone calnexin
AU - Li, Feng
AU - Mandal, Mahitosh
AU - Barnes, Christopher J.
AU - Vadlamudi, Ratna K.
AU - Kumar, Rakesh
N1 - Funding Information:
This study was supported in part by NIH Grants CA80066 and CA65746 and the Breast Cancer Research Program of the University of Texas M. D. Anderson Cancer Center. We thank Larry W. Tjoelker for calnexin cDNA.
PY - 2001/12/7
Y1 - 2001/12/7
N2 - Heregulin-β1 (HRG) is a regulatory polypeptide having several distinct biological effects in mammary epithelial cells. To address the hypothesis that HRG selectively regulates gene expression, we performed differential display screening using cells grown in the presence or absence of HRG. One cDNA clone upregulated by HRG was identical to human calnexin, a protein with molecular chaperone function. This is the first demonstration of the regulation of calnexin mRNA and protein expression by a physiologically relevant polypeptide factor in human breast cancer cells. HRG stimulation also caused a rapid redistribution of calnexin from vesicle-like structures in the cell cytoplasm to the perinuclear area and to the cell membrane. Furthermore, HRG induced colocalization and physical interaction of calnexin with the HER2 growth factor receptor. Finally, calnexin protein levels were increased in progressive stages of human breast cancer. These findings suggest that stimulation of calnexin expression by HRG may constitute a mechanism of protein redistribution and facilitate downstream signaling events in growth-factor-activated cells.
AB - Heregulin-β1 (HRG) is a regulatory polypeptide having several distinct biological effects in mammary epithelial cells. To address the hypothesis that HRG selectively regulates gene expression, we performed differential display screening using cells grown in the presence or absence of HRG. One cDNA clone upregulated by HRG was identical to human calnexin, a protein with molecular chaperone function. This is the first demonstration of the regulation of calnexin mRNA and protein expression by a physiologically relevant polypeptide factor in human breast cancer cells. HRG stimulation also caused a rapid redistribution of calnexin from vesicle-like structures in the cell cytoplasm to the perinuclear area and to the cell membrane. Furthermore, HRG induced colocalization and physical interaction of calnexin with the HER2 growth factor receptor. Finally, calnexin protein levels were increased in progressive stages of human breast cancer. These findings suggest that stimulation of calnexin expression by HRG may constitute a mechanism of protein redistribution and facilitate downstream signaling events in growth-factor-activated cells.
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U2 - 10.1006/bbrc.2001.6001
DO - 10.1006/bbrc.2001.6001
M3 - Article
C2 - 11726208
AN - SCOPUS:0035824393
SN - 0006-291X
VL - 289
SP - 725
EP - 732
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -