Autocrine stimulation of AR4-2J rat pancreatic tumor cell growth by glycine-extended gastrin
✍ Scribed by Fabrice Nègre; Pierrette Fagot-Revurat; Michèle Bouisson; Jens F. Rehfeld; Nicole Vaysse; Lucien Pradayrol
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 695 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Glycine-extended gastrin (gastrin-Gly) stimulates proliferation of AR4-2) pancreatic tumor cell line through a specific receptor, different from the gastrin-cholecystokinin B receptor. Our purpose was to determine whether AR4-2) cells produced gastrin-Gly and then whether the peptide was involved in an autocrine loop. First, proliferation of AR4-2) 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 a-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 a-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 AR4-2) cells and that it participates with EGF in the regulation of AR4-2)-cell proliferation.