ISSN:
0730-2312
Keywords:
carcinoma
;
autocrine stimulation
;
EGF-receptor
;
transforming growth factor
;
autocrine function
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Carcinoma cells frequently coexpress transforming growth factor (TGF)-α and its receptor, the epidermal growth factor (EGF) receptor, implicating an autocrine function of carinoma-derived TGF-α. Using a monoclonal antibody (425) to the EGF-receptor, we investigated the role of exogenous and tumor cell-derived EGF/TGF-α mitogenic activities in proliferation of cell lines derived from solid tumors. Monoclonal antibody 425 was chosen for these studies because it inhibits binding of EGF/TGF-α to the EGF-receptor and effectively blocks activation of the EGF-receptor by EGF/TGF-α. Seven malignant cell lines originating from carcinomas of colon, pancreas, breast, squamous epithelia, and bladder expressed surface EGF-receptor and secreted EGF/TGF-α-like mitogenic activities into their tissue culture media. All cell lines were maintained in a defined medium free of exogenous EGF/TGF-α. EGF and TGF-α added to the culture medium stimulated proliferation of five cell lines to comparable levels. EGF/TGF-α-dependent proliferation was significantly reduced by addition of MAb 425 to culture media. In addition, monoclonal antibody 425 reduced proliferation of the five EGF/TGF-α responsive cell lines in the absence of exogenous EGF/TGF-α. Antiproliferative effects induced by monoclonal antibody 425 were reversible and could be overcome by addition of EGF to culture media. Our results indicate that tumor-derived EGF-receptor-reactive mitogens can promote proliferation of carcinoma cells in an autocrine fashion.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240440202
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