AUTOCRINE GROWTH-STIMULATION OF SW403 COLON-CARCINOMA CELL-LINE IS CAUSED BY TRANSFORMING-GROWTH-FACTOR-ALPHA-MEDIATED EPIDERMAL GROWTH-FACTOR RECEPTOR ACTIVATION
T. Hirsch et al., AUTOCRINE GROWTH-STIMULATION OF SW403 COLON-CARCINOMA CELL-LINE IS CAUSED BY TRANSFORMING-GROWTH-FACTOR-ALPHA-MEDIATED EPIDERMAL GROWTH-FACTOR RECEPTOR ACTIVATION, Journal of cancer research and clinical oncology, 122(6), 1996, pp. 328-334
Results of recent studies indicate that some cultured human carcinoma
cell lines are capable of proliferating autonomously in serum-free med
ium as a result of the synthesis and secretion of transforming growth
factor alpha (TGF alpha). TGF alpha interacts with epidermal growth fa
ctor receptor (EGFR) and induces its activation. In an attempt to exte
nd these observations, we evaluated TGF alpha-mediated autonomous grow
th and constitutive EGFR activation in the human adenocarcinoma cell l
ine SW403. The cell line shows synthesis of EGF receptors and TGF alph
a but not EGF, and exhibits constitutive phosphorylation of the 170-kD
a EGFR. Use of blocking anti-EGFR monoclonal antibodies (mAb) inhibits
autonomous growth of SW403 cells and leads to a significant reduction
of receptor phosphorylation. The inhibitory effect of the blocking an
ti-EGFR mAb is reversible upon addition of TGF alpha. In contrast, aut
onomous proliferation of SW403 cells is not inhibited by addition of n
eutralizing anti-EGF mAb. Our findings suggest that the proliferation
of cells of the human SW403 adenocarcinoma cell line is regulated by a
n autocrine TGF alpha loop and that this regulatory pathway can be int
errupted by using anti-EGFR mAb.