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IGF-II/IGF-I receptor pathway up-regulates COX-2 mRNA expression and PGE2 synthesis in Caco-2 human colon carcinoma

A Di Popolo1, A Memoli, A Apicella

  • 1Dipartimento di Biologia e Patologia Cellulare e Molecolare, L Califano, Centro di Endocrinologia ed Oncologia Sperimentale G. Salvatore del Consiglio Nazionale delle Ricerche, Università Federico II, Napoli, Italy.

Oncogene
|December 15, 2000
PubMed

Insights

Nonsteroidal anti-inflammatory drugs lower colon cancer risk by inhibiting cyclo-oxygenase-2 (COX-2). This study shows insulin-like growth factor-II (IGF-II) up-regulates COX-2 via the IGF-I receptor pathway in colon cancer cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to reduce colon cancer risk.
  • This protective effect is partly mediated by the inhibition of cyclo-oxygenase-2 (COX-2).
  • Insulin-like growth factor-II (IGF-II) plays a role in cell proliferation and tumor progression.

Purpose of the Study:

  • To investigate the role of the IGF-II/IGF-I receptor pathway in regulating COX-2 expression and prostaglandin E2 (PGE2) synthesis in colon carcinoma cells.
  • To elucidate the molecular mechanisms linking IGF-II signaling to COX-2 up-regulation.

Main Methods:

  • Utilized Caco-2 colon carcinoma cell line.
  • Measured COX-2 mRNA and PGE2 levels in proliferating versus differentiated cells.
  • Investigated the effect of IGF-II overexpression and IGF-I receptor blockade (antibody and dominant-negative receptor) on COX-2 expression.
  • Examined the role of PI3-kinase signaling pathway.

Main Results:

  • COX-2 expression and PGE2 synthesis are up-regulated by an IGF-II/IGF-I receptor autocrine pathway in Caco-2 cells.
  • Elevated COX-2 and PGE2 levels were observed in proliferating cells and cells overexpressing IGF-II.
  • IGF-II-induced COX-2 up-regulation is mediated through IGF-I receptor activation and PI3-kinase signaling.
  • COX-2 expression inversely correlated with apoptosis.

Conclusions:

  • The IGF-II/IGF-I receptor pathway promotes colon cancer cell proliferation and tumor progression partly through the activation of COX-2.
  • Targeting the IGF-II/IGF-I receptor-COX-2 axis may offer therapeutic strategies for colon cancer.

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