Insulin-like growth factor I receptors are expressed by the enteroendocrine cell line STC-1: relationship with proliferation and cholecystokinin expression.
Receptors for insulin-like growth factors (IGF-I and IGF-II) are expressed in mammalian intestinal epithelium. No information on the presence of IGF receptors in intestinal endocrine cells is available. We tested for IGF-I receptors the endocrine cell line STC-1, which synthesizes and processes cholecystokinin (CCK) among other peptides, and assessed the effects of IGF-I on cell growth and CCK content. Cell monolayers in serum-free culture medium specifically bound [125I]IGF-I. Scatchard analysis was consistent with a single class of high affinity binding sites (KD = 0.91 nM; Bmax = 4,700 sites/cell). In competitive binding assays, unlabeled IGF-I, IGF-II and insulin displaced in a dose-dependent manner [125I]IGF-I binding with the following potencies (KI): IGF-I (0.74 nM) > IGF-II (3 nM) >> insulin (1 microM). Affinity cross-linking with [125I]IGF-I using disuccinimidyl suberate and SDS-PAGE under reducing conditions yielded a polypeptide band with apparent Mr 130,000, consistent with the alpha-subunit of the IGF-I receptor. IGF-I and IGF-II (0.3-30 nM) dose-dependently stimulated [3H]thymidine incorporation, with a maximal response of 110% above basal. IGF-II was approximately 10-fold less potent than IGF-I, suggesting a mediation through IGF-I receptors. In addition, the numbers of cells treated with 3 nM IGF-I amounted to 116, 130 and 159% of control values after 1, 2 and 4 days of incubation, respectively (p < 0.05). A significant increase in the cell CCK contents was observed after a 48-hour exposure to 3 or 30 nM IGF-I. These results demonstrate IGF-I receptor expression by the enteroendocrine cell line STC-1. IGF-I stimulates proliferation in short-term experiments, and increases intracellular levels of CCK.
INSERM Unité 45, Hôpital Edouard-Herriot, Lyon, France.
F
F
Ye
A M
AM
Chevrier
D
D
Langlois
J C
JC
Cuber
J M
JM
Saez
J A
JA
Chayvialle
J
J
Abello
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002766:Cholecystokinin / Q000378:metabolism; D004702:Endocrine Glands / Q000166:cytology / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D007334:Insulin-Like Growth Factor I; D002766:Cholecystokinin; D017526:Receptor, IGF Type 1