TY - JOUR
T1 - Autocrine stimulation of AR4-2J rat pancreatic tumor cell growth by glycine-extended gastrin
AU - Nègre, F
AU - Fagot-Revurat, P
AU - Bouisson, M
AU - Rehfeld, J F
AU - Vaysse, N
AU - Pradayrol, L
PY - 1996/5/29
Y1 - 1996/5/29
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Antibodies/pharmacology
KW - Cell Division/drug effects
KW - Epidermal Growth Factor/pharmacology
KW - Gastrins/biosynthesis
KW - Gene Expression
KW - Humans
KW - Molecular Sequence Data
KW - Oligonucleotides, Antisense/pharmacology
KW - Pancreatic Neoplasms/metabolism
KW - Rats
KW - Stimulation, Chemical
KW - Thionucleotides/pharmacology
KW - Tumor Cells, Cultured/drug effects
U2 - 10.1002/(SICI)1097-0215(19960529)66:5<653::AID-IJC12>3.0.CO;2-5
DO - 10.1002/(SICI)1097-0215(19960529)66:5<653::AID-IJC12>3.0.CO;2-5
M3 - Journal article
C2 - 8647628
SN - 0020-7136
VL - 66
SP - 653
EP - 658
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -