Growth stimulation by transfection of intestinal epithelial cells with an antisense insulin-like growth factor binding protein-2 construct.
IEC-6 cells, an intestinal epithelial cell line, produce insulin-like growth factor (IGF)-II and IGF-binding protein-2 (IGFBP-2). Exogenous IGFs stimulate and IGFBP-2 attenuates DNA synthesis. To investigate whether endogenously secreted IGFBP-2 inhibits proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA antisense expression construct. The steady-state level of IGFBP-2 mRNA decreased by 54% in the antisense cDNA-transfected cells (denoted revBP2) compared with vector-transfected controls. Moreover, revBP2 cells secreted less IGFBP-2 than controls (maximally a 68% decrease). In serum-containing medium, revBP2 cells exhibited a 35% increase in log-phase proliferation rate and growth-arrested at a maximum density 14% higher than controls. We conclude that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs.
Corkins
M R
MR
Department of Pediatrics, Creighton University, Omaha, NE 68198, USA.
Vanderhoof
J A
JA
Slentz
D H
DH
MacDonald
R G
RG
Park
J H
JH
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development; D018971:Insulin-Like Growth Factor Binding Protein 2; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D002352:Carrier Proteins; D016373:DNA, Antisense; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D013002:Somatomedins; D007335:Insulin-Like Growth Factor II