[Gastrin-17 and G17-gly induce proliferation of LoVo cells through the CCK B/gastrin receptor].
METHODS
Recent studies suggest that glycine-extended gastrin (G17-gly) stimulates in vitro proliferation of the pancreatic cell line AR4-2J, through selective receptors distinct from the CCK-B/G-receptor mediating the effects of amidated gastrin (G17). The aims of our study were to examine the effects of G17 and G17-gly on the growth of the colorectal cancer cell line LoVo and to determine the receptor involved by using selective receptor-antagonist.


RESULTS
Both G17 and G17-gly stimulated [3H]-thymidine incorporation in a concentration-dependent fashion. Maximal stimulation (153 +/- 18% and 166 +/- 17% of control, p < 0.01) was achieved with 10 nM G17 and 100 nM G17-gly, respectively. These stimulations were fully prevented by the presence of 10 pM YM022, a G/CCK B receptor-antagonist, but unaffected by L364,718, a CCK A receptor-antagonist. Basal growth of LoVo cells was inhibited by YM022 and stimulated by L364,718. CCK A and G/CCK B receptors mRNA were detected in the cells. Gastrin immunoreactivity was detected in the cells (16 pM) and in the extracellular medium (4.5 pM).


CONCLUSIONS
Both G17 and G17-gly stimulate LoVo cells growth through the activation of a gastrin/CCK B receptor. The evidence for secreted gastrin and CCK A and B receptors mRNA may further suggest the existence of an autocrine loop involving a stimulatory gastrin/CCK B receptor.
Artru
P
P
INSERM U10, Hôpital Bichat-Claude Bernard, Paris.
Attoub
S
S
Levasseur
S
S
Lewin
M J
MJ
Bado
A
A
D001569:Benzodiazepines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D005755:Gastrins; D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C086854:glycine-extended gastrin 17; D001569:Benzodiazepines; C087260:YM 022; C013550:gastrin 17
La G17 et la G17-gly stimulent la prolifération des cellules LoVo par l'intermédiaire du récepteur CCK B/gastrine.