Inhibition of Caco-2 cell proliferation by all-trans retinoic acid

Role of insulin-like growth factor binding protein-6

Eun J. Kim, Young Hee Kang, Beverly S. Schaffer, Leon A. Bach, Richard G MacDonald, Jung H Y Park

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The present study examined the effects of all-trans retinoic acid (tRA) on proliferation and expression of the IGF system in Caco-2 human colon adenocarcinoma cells. tRA inhibited Caco-2 cell proliferation in a dose-dependent manner, with a 40±2% decrease in cell number observed 48 h after the addition of 1 μM tRA. Ligand blot analysis of IGFBPs in conditioned media revealed that Caco-2 cells produced three IGFBPs of Mr: 34,000 (IGFBP-2), 24,000 (IGFBP-4), and 32,000 (IGFBP-6). The concentrations of IGFBP-2 and IGFBP-4 decreased by 48±6 and 70±13%, respectively, whereas that of IGFBP-6 increased by 698±20% with 1 -M tRA. tRA decreased mRNA levels of IGFBP-2 and IGFBP-4 by 20±3 and 50±8%, respectively, whereas tRA increased IGFBP-6 mRNA by 660±20%. tRA did not alter levels of IGF-II mRNA or peptide. To examine if endogenous IGFBP-6 inhibits cell proliferation, Caco-2 cells were transfected with an IGFBP-6 CDNA expression construct or pcDNA3 vector only and stable clones were selected. Clones overexpressing IGFBP-6 grew more slowly than vector controls and achieved final densities 30-55% lower than those of vector controls. Accumulation of IGFBP-6 mRNA and concentrations of IGFBP-6 peptide in conditioned media were increased by 200-250 and 220-250%, respectively, in the IGFBP-6 clones compared with controls. Increased expression of IGFBP-6, which has a high binding affinity for IGF-II, following tRA treatment suggests that the decreased proliferation caused by tRA may result, at least in part, from IGFBP-6-mediated disruption of the IGF-II autocrine loop in these colon cancer cells.

Original languageEnglish (US)
Pages (from-to)92-100
Number of pages9
JournalJournal of Cellular Physiology
Volume190
Issue number1
DOIs
StatePublished - Jan 1 2002

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Insulin-Like Growth Factor Binding Protein 6
Caco-2 Cells
Cell proliferation
Tretinoin
Cell Proliferation
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor II
Insulin-Like Growth Factor Binding Proteins
Messenger RNA
Clone Cells
Conditioned Culture Medium
Peptides
Colonic Neoplasms

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Inhibition of Caco-2 cell proliferation by all-trans retinoic acid : Role of insulin-like growth factor binding protein-6. / Kim, Eun J.; Kang, Young Hee; Schaffer, Beverly S.; Bach, Leon A.; MacDonald, Richard G; Park, Jung H Y.

In: Journal of Cellular Physiology, Vol. 190, No. 1, 01.01.2002, p. 92-100.

Research output: Contribution to journalArticle

Kim, Eun J. ; Kang, Young Hee ; Schaffer, Beverly S. ; Bach, Leon A. ; MacDonald, Richard G ; Park, Jung H Y. / Inhibition of Caco-2 cell proliferation by all-trans retinoic acid : Role of insulin-like growth factor binding protein-6. In: Journal of Cellular Physiology. 2002 ; Vol. 190, No. 1. pp. 92-100.
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abstract = "The present study examined the effects of all-trans retinoic acid (tRA) on proliferation and expression of the IGF system in Caco-2 human colon adenocarcinoma cells. tRA inhibited Caco-2 cell proliferation in a dose-dependent manner, with a 40±2{\%} decrease in cell number observed 48 h after the addition of 1 μM tRA. Ligand blot analysis of IGFBPs in conditioned media revealed that Caco-2 cells produced three IGFBPs of Mr: 34,000 (IGFBP-2), 24,000 (IGFBP-4), and 32,000 (IGFBP-6). The concentrations of IGFBP-2 and IGFBP-4 decreased by 48±6 and 70±13{\%}, respectively, whereas that of IGFBP-6 increased by 698±20{\%} with 1 -M tRA. tRA decreased mRNA levels of IGFBP-2 and IGFBP-4 by 20±3 and 50±8{\%}, respectively, whereas tRA increased IGFBP-6 mRNA by 660±20{\%}. tRA did not alter levels of IGF-II mRNA or peptide. To examine if endogenous IGFBP-6 inhibits cell proliferation, Caco-2 cells were transfected with an IGFBP-6 CDNA expression construct or pcDNA3 vector only and stable clones were selected. Clones overexpressing IGFBP-6 grew more slowly than vector controls and achieved final densities 30-55{\%} lower than those of vector controls. Accumulation of IGFBP-6 mRNA and concentrations of IGFBP-6 peptide in conditioned media were increased by 200-250 and 220-250{\%}, respectively, in the IGFBP-6 clones compared with controls. Increased expression of IGFBP-6, which has a high binding affinity for IGF-II, following tRA treatment suggests that the decreased proliferation caused by tRA may result, at least in part, from IGFBP-6-mediated disruption of the IGF-II autocrine loop in these colon cancer cells.",
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