Overexpression of epidermal growth factor and insulin-like growth factor-I receptors and autocrine stimulation in human esophageal carcinoma cells.
The growth-stimulatory effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and insulin-like growth factor-I (IGF-I) on the human esophageal carcinoma cell line CE48T/VGH were evaluated. Under serum-free conditions, EGF, TGF-alpha, and IGF-I promoted 3.6- to 4.1-fold increased cell proliferation. Scatchard analyses and Northern blot hybridization revealed that both the EGF/TGF-alpha receptor and the IGF-I receptor were overexpressed in CE48T/VGH cells. Furthermore, ligand-dependent autophosphorylation of the EGF receptor and the IGF-I receptor was clearly detected using antireceptor and antiphosphotyrosine antibodies. Autocrine regulation was strongly indicated by the following evidence: (a) CE48T/VGH cells were found to express TGF-alpha and IGF-I genes, (b) serum-free conditioned medium promoted the growth of CE48T/VGH cells and stimulated the autophosphorylation of the EGF/TGF-alpha receptor and the IGF-I receptor, and (c) the addition of IGF-I receptor antibodies significantly suppressed CE48T/VGH cell growth under serum-free conditions. Our studies suggest that the overexpression of EGF and IGF-I receptors and autocrine growth regulation may concertedly control the proliferation of esophageal carcinoma cells.
Chen
S C
SC
Graduate Institute of Microbiology and Immunology, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China.
Chou
C K
CK
Wong
F H
FH
Chang
C M
CM
Hu
C P
CP
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016211:Transforming Growth Factor alpha; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors