The role of transforming growth factor alpha in the enterochromaffin-like cell tumor autonomy in an African rodent mastomys.
OBJECTIVE
Gastric carcinoids evolved from enterochromaffin-like (ECL) cell hyperplasia are usually associated with high pH and hypergastrinemia. The Mastomys species exhibits a genetic propensity to gastric carcinoid formation that can be accelerated by acid inhibition-induced hypergastrinemia. Although gastrin is critical in the initiation of the ECL cell transformation, the role of other growth factors involved in the evolution of the tumor autonomy has not been established. The aim of this study was to evaluate the role of transforming growth factor (TGF) alpha in the regulation of ECL cell transformation.


METHODS
Mastomys were orally administered an irreversible H2-receptor antagonist loxtidine for 0, 8, and 16 weeks, and ECL cell transformation was monitored by assessing gastrin levels, mucosal histamine content, and chromogranin immunoreactivity. The ECL cells were purified, and cell proliferation at each stage in response to gastrin and TGF alpha was measured by bromodeoxyuridine uptake. TGF-alpha expression was evaluated by radioimmunoassay and Northern blot, and epidermal growth factor (EGF) receptor expression was determined by Western blot, immunoprecipitation, and immunocytochemistry.


RESULTS
Although the response to gastrin decreased during hypergastrinemia, the proliferative effect of TGF-alpha on ECL cells was specifically amplified during the development of hyperplasia. TGF-alpha and EGF receptor expression increased steadily in the transformed cells.


CONCLUSIONS
During low acid-induced hypergastrinemia, the expression of TGF-alpha and EGF receptor may constitute an autocrine regulatory mechanism in ECL cell tumor transformation.
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
L H
LH
Tang
I M
IM
Modlin
G P
GP
Lawton
M
M
Kidd
R
R
Chinery
D000818:Animals; D002276:Carcinoid Tumor / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004759:Enterochromaffin Cells / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005755:Gastrins / Q000097:blood; D006632:Histamine / Q000032:analysis; D009115:Muridae; D013274:Stomach Neoplasms / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000502:physiology*
D005755:Gastrins; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D006632:Histamine; D066246:ErbB Receptors