Constitutive insulin-like growth factor-II expression interferes with the enterocyte-like differentiation of CaCo-2 cells

Raffaele Zarrilli, Marco Romano, Sandro Pignata, Stefano Casola, Carmelo B. Bruni, Angela M. Acquaviva

Research output: Contribution to journalArticle

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Abstract

In this study we have examined the role of insulin-like growth factor-II (IGF-II) in the differentiation of the CaCo-2 human colon carcinoma cell line. We have shown previously that IGF-II is an autocrine growth factor for CaCo-2 cells. IGF-II expression is high in proliferating, undifferentiated CaCo-2 cells and markedly decreases when cells become confluent and start to differentiate. To evaluate whether differentiation of CaCo-2 cells depends on an IGF-II related pathway, we treated cells with a blocking antibody to the IGF-I receptor that mediates most IGF-II biological effects. Treatment of preconfluent CaCo-2 cells with this antibody decreased by 40% autonomous cell proliferation and induced differentiation as shown by an increase in sucrase isomaltase activity and apolipoprotein A-I (apoA-I) mRNA levels. To examine the significance of autocrine IGF-II production in CaCo-2 cell differentiation, we generated stable CaCo-2 cell lines that constitutively express rat IGF-II under the control of a Rous sarcoma virus promoter. Sustained expression of IGF-II resulted in: (a) increased proliferative rate; (b) high IGF-I receptor number, even after reaching confluence; (c) increased capability of anchorage-independent growth; (d) inhibition of the expression of apoA-I and SI mRNAs. Analysis of several independent IGF-II-transfected clones showed an inverse correlation between IGF-II mRNA levels and expression of the differentiation markers, the cells expressing the higher levels of the transfected IGF-II being the less differentiated ones. Our data suggest that perturbation of IGF-II-mediated cell proliferation interferes with the enterocyte-like differentiation pathway of CaCo-2 cells.

Original languageEnglish
Pages (from-to)8108-8114
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number14
DOIs
Publication statusPublished - Apr 5 1996

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Insulin-Like Growth Factor II
Caco-2 Cells
Enterocytes
IGF Type 1 Receptor
Apolipoprotein A-I
Cells
Cell proliferation
Messenger RNA
Oligo-1,6-Glucosidase
Cell Proliferation
Sucrase
Rous sarcoma virus
Cell Line
Blocking Antibodies
Differentiation Antigens
Viruses
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Colon
Clone Cells

ASJC Scopus subject areas

  • Biochemistry

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Constitutive insulin-like growth factor-II expression interferes with the enterocyte-like differentiation of CaCo-2 cells. / Zarrilli, Raffaele; Romano, Marco; Pignata, Sandro; Casola, Stefano; Bruni, Carmelo B.; Acquaviva, Angela M.

In: Journal of Biological Chemistry, Vol. 271, No. 14, 05.04.1996, p. 8108-8114.

Research output: Contribution to journalArticle

Zarrilli, Raffaele ; Romano, Marco ; Pignata, Sandro ; Casola, Stefano ; Bruni, Carmelo B. ; Acquaviva, Angela M. / Constitutive insulin-like growth factor-II expression interferes with the enterocyte-like differentiation of CaCo-2 cells. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 14. pp. 8108-8114.
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