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Growth modulation by epidermal growth factor (EGF) in human colonic carcinoma cells: Constitutive expression of the human EGF gene
Author(s) -
Huang Shuang,
Lin PinFang,
Fan Dominic,
Price Janet E.,
Trujillo Jose M.,
Chakrabarty Subhas
Publication year - 1991
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041480206
Subject(s) - epidermal growth factor , cancer research , modulation (music) , gene expression , heparin binding egf like growth factor , growth factor , colonic carcinoma , microbiology and biotechnology , biology , gene , chemistry , carcinoma , cell culture , receptor , biochemistry , genetics , physics , acoustics
The functional role of epidermal growth factor (EGF) in epithelium‐derived human colonic carcinoma cells was investigated by transfection with plasmid pUCDS3, which contained synthetic human EGF encoding sequences, into two human colonic carcinoma cell types with dissimilar phenotypic properties: the moderately differentiated and growth factor‐responsive Moser and the highly metastatic KM12SM cells. The Moser cells exhibited a proliferative response to treatment with exogenous EGF, while the KM12SM cells did not. The constitutive expression of the human EGF gene in these colonic carcinoma cell types resulted in elevated expression of EGF mRNA, with concurrent production and secretion of a large amount of EGF, and downmodulation of transforming growth factor‐alpha (TGF‐alpha) secretion. Growth stimulation and down‐modulation of both high and low affinity EGF receptors were observed in the EGF‐transfected Moser clones. Results of experiments using anti‐EGF and anti‐EGF‐receptor antibody to block the proliferation of EGF‐transfected Moser clones suggested that autocrine stimulatory mechanisms involving both EGF and TGF‐alpha were operative in these cells. By comparison, a growth‐inhibitory effect, with no apparent EGF receptor modulation, was observed in the EGF‐transfected KM12SM clones. Both the parental and EGF‐transfected KM12SM clones possessed fewer EGF receptors than the Moser cells, and anti‐EGF or anti‐EGF‐receptor antibody did not affect the cells' growth properties. These results suggested that the mechanisms of growth inhibition in the EGF‐transfected KM12SM clones were non‐autocrine or intracellular in nature. Thus, constitutive expression of the human EGF gene in two phenotypically different, epithelium‐derived human colonic carcinoma cells resulted in divergent altered growth characteristics.