Regulation of the insulin-like growth factor axis by increasing cell number in intestinal epithelial (IEC-6) cells.
Insulin-like growth factor binding protein-2 (IGFBP-2) production as a function of cell number by intestinal epithelial cells (IEC-6) was regulated such that the IGFBP-2 concentration in 24-h conditioned medium reached a maximum, which was maintained despite increasing cell number. Northern blot analysis revealed that this effect could largely be attributed to decreasing IGFBP-2 mRNA. In contrast to IGFBP-2, secretion of IGF-II and accumulation of IGF-II mRNA by IEC-6 cells correlated positively with cell number. The highest level of IGF-II protein detected by immunoblotting of conditioned medium occurred in post-confluent cells. IGF-I stimulated the cells to grow to a high cellular density and inhibited IGFBP-2 secretion in a concentration-dependent fashion. We conclude that expression of IGF-II and IGFBP-2 are regulated in IEC-6 cells by cellular density, and IGF-II may act as a survival factor at high cell density.
Corkins
M R
MR
Department of Pediatrics, Division of Pediatric Gastroenterology, University of Nebraska Medical Center/Creighton University, USA. MRCorkin@pol.net
Park
J H
JH
Davis
D V
DV
Slentz
D H
DH
MacDonald
R G
RG
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D007422:Intestines; D007457:Iodine Radioisotopes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D017077:Culture Media, Conditioned; D018971:Insulin-Like Growth Factor Binding Protein 2; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II