Growth stimulation by coexpression of transforming growth factor-alpha and epidermal growth factor-receptor in normal and adenomatous human colon epithelium.
Autocrine stimulation of the epidermal growth factor receptor (EGF-R), by coexpression of transforming growth factor-alpha (TGF-alpha), causes malignant transformation of some fibroblast cell lines. TGF-alpha and EGF-R are both known to be expressed in colon carcinoma tissue and have been shown coexpressed in colon carcinoma cell lines. TGF-alpha autocrine activation of EGF-R has been suggested as a potential mechanism contributing to abnormal growth control in colon cancer. We now report coexpression of TGF-alpha and EGF-R transcripts in morphologically normal colonic epithelium from five individuals, in colonic adenomas from three individuals, and in a nontumorigenic colon adenoma cell line, VACO-330. Functional studies demonstrate VACO-330 growth is stimulated by exogenous TGF-alpha and is completely abolished by a blocking anti-EGF-R antibody. Autocrine stimulation of EGF-R by TGF-alpha is therefore required for growth of the adenoma cell line. Autocrine stimulation of EGF-R by TGF-alpha does not cause malignant transformation of the colonic epithelial cell. In normal and adenomatous human colon TGF-alpha, via either an autocrine or paracrine mechanism, is likely an important physiologic stimulant of epithelial proliferation.
Markowitz
S D
SD
Ireland Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106.
Molkentin
K
K
Gerbic
C
C
Jackson
J
J
Stellato
T
T
Willson
J K
JK
D000236:Adenoma / Q000473:pathology*; D015152:Blotting, Northern; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D066246:ErbB Receptors / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D015291:Transforming Growth Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D015291:Transforming Growth Factors; D066246:ErbB Receptors