Autocrine stimulation of AR4-2J rat pancreatic tumor cell growth by glycine-extended gastrin

F Nègre, P Fagot-Revurat, M Bouisson, J F Rehfeld, N Vaysse, L Pradayrol

Abstract

Glycine-extended gastrin (gastrin-Gly) stimulates proliferation of AR4-2J pancreatic tumor cell line through a specific receptor, different from the gastrin-cholecystokinin B receptor. Our purpose was to determine whether AR4-2J cells produced gastrin-Gly and then whether the peptide was involved in an autocrine loop. First, proliferation of AR4-2J cells in serum-free medium was inhibited by a gastrin anti-sense oligodeoxynucleotide phosphorothioate and by antibodies specific for gastrin-Gly. In contrast, antibodies specific for alpha-amidated gastrin were without effect. By using RT-PCR, we have shown that AR4-2J cells expressed gastrin mRNA. The presence of gastrin-Gly, but not alpha-amidated gastrin, in serum-free media was detected by radioimmunoanalysis. Gel chromatography revealed that the predominant molecular forms secreted were glycine-extended gastrin-34 and gastrin- 17. Furthermore, epidermal growth factor (EGF), a stimulator of gastrin gene transcription, modulates gastrin-Gly secretion by AR4-2J. These data together suggest that gastrin-Gly is an autocrine growth factor for AR4-2J cells and that it participates with EGF in the regulation of AR4-2J-cell proliferation.

OriginalsprogEngelsk
TidsskriftInternational Journal of Cancer
Vol/bind66
Udgave nummer5
Sider (fra-til)653-8
Antal sider6
ISSN0020-7136
DOI
StatusUdgivet - 29 maj 1996
Udgivet eksterntJa

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