Coordinate expression of insulin-like growth factor II (IGF-II) and IGF-II/mannose-6-phosphate receptor mRNA and stable expression of IGF-I receptor mRNA during differentiation of human colon carcinoma cells (Caco-2)

被引:17
作者
Hoeflich, A
Yang, Y
Rascher, W
Blum, WF
Huber, S
Koepf, G
Kolb, HJ
Kiess, W
机构
[1] UNIV GIESSEN,CHILDRENS HOSP,D-35385 GIESSEN,GERMANY
[2] SHANGHAI MED UNIV,CHILDRENS HOSP,SHANGHAI 200032,PEOPLES R CHINA
[3] UNIV MUNICH,DEPT PHYSIOL,D-8000 MUNICH,GERMANY
[4] HARLACHING CITY HOSP,DEPT CLIN CHEM,MUNICH,GERMANY
关键词
D O I
10.1530/eje.0.1350049
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Insulin-like growth factor II (IGF-II) has been implicated in the differentiation of skeletal muscle cells. In this study the putative role of IGF-II in epithelial cell differentiation was investigated. The expression of IGF-IT, IGF-I receptor and IGP-II/mannose-6-phosphate receptor (IGF-II/M6P receptor) mRNA during spontaneous differentiation of the colon carcinoma cell line Caco-2 was measured. In addition, differentiation of Caco-2 cells during the cell culture period (days 1-21 in culture) was studied in parallel using morphological (light and scanning electron microscopy) and biochemical markers of growth (DNA, RNA and protein content, and beta-actin mRNA and glyceraldehyde phosphate dehydrogenase mRNA expression) and differentiation (alkaline phosphatase activity, carcinoembryonic antigen content). A putative correlation between the markers of growth and differentiation and IGF gene expression was studied using linear regression analysis. Expression of IGF-II mRNA and IGF-II/M6P receptor mRNA correlated significantly with the progress of differentiation, while the IGF-I receptor was stably expressed throughout the culture period and exhibited a crucial role for the survival of Caco-2 cells, as shown by blocking experiments employing the monoclonal anti-IGF-I receptor antibody alpha-IRS. We hypothesize that: IGF-II mRNA and IGF-II-/M6P receptor mRNA are expressed in a coordinate fashion during the differentiation of Caco-2 cells; coordinate expression of IGF-II and of IGF-II/M6P receptor mRNA might point to a role for ICE-Il as a growth stimulant and for the IGF-II/M6P receptor for a regulator of ICE-II bioavailability in differentiating cells; alternatively, high IGF-II/M6P receptor mRNA and protein expression in differentiated cells but low IGF-IT binding to the IGF-II/M6P receptor point to an important intracellular role of this receptor type in differentiated colon epithelial cells; the IGF-I receptor mRNA is stably expressed during the differentiation process of Caco-2 cells; the ICE-I receptor protein seems to be a prerequisite for the survival of Caco-2 cells.
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页码:49 / 59
页数:11
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