Expression of IGFBP-2, -3, and -4 mRNA during differentiation of Caco-2 colon epithelial cells.
Local production of insulin-like growth factor (IGF)-binding proteins (IGFBP) determines the availability of the IGF to the cell and thus regulates IGF action. To find out whether specific patterns of IGFBP gene expression and IGFBP secretion were related to cell growth vs. cell differentiation, expression of IGFBP during long-term culture (21 days, n = 5) of the colon carcinoma cell line Caco-2 was investigated at the mRNA and protein levels. Markers of cell proliferation (increase in DNA, RNA, and protein content) and of differentiation [alkaline phosphatase (AP) activity; creatine kinase (CK) activity] were measured in parallel during long-term culture. IGFBP-2 mRNA expression correlated significantly with markers of proliferation (P < 0.05), whereas IGFBP-3 mRNA expression or IGFBP-3 secretion correlated with markers of differentiation (AP: r = 0.83, P < 0.001; CK: r = 0.45, P < 0.01). Similarly, IGFBP-4 mRNA expression correlated significantly with markers of differentiation (AP: r = 0.34, P < 0.05; CK: r = 0.35, P < 0.05). We hypothesize that IGFBP-3 and -4 are related to differentiation of Caco-2 cells, whereas IGFBP-2 is related to proliferation in Caco-2 cells.
Hoeflich
A
A
Children's Hospital, Justus Liebig University, Giessen, Germany.
Yang
Y
Y
Huber
S
S
Rascher
W
W
Koepf
G
G
Blum
W F
WF
Heinz-Erian
P
P
Kolb
H J
HJ
Kiess
W
W
D000469:Alkaline Phosphatase / Q000378:metabolism; D018938:Caco-2 Cells; D002454:Cell Differentiation; D002455:Cell Division; D003402:Creatine Kinase / Q000378:metabolism; D015342:DNA Probes; D004847:Epithelial Cells; D004848:Epithelium / Q000648:ultrastructure; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis*; D008855:Microscopy, Electron, Scanning; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D003402:Creatine Kinase; D000469:Alkaline Phosphatase