Cyclooxygenase-2 Modulates the Insulin-Like Growth Factor Axis in Non–Small-Cell Lung Cancer
- 15 September 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 64 (18) , 6549-6555
- https://doi.org/10.1158/0008-5472.can-04-1225
Abstract
Constitutive overexpression of cyclooxygenase-2 (COX-2) occurs frequently in several different malignancies, including lung, colon, breast, and prostate cancer. Clinical studies have established elevated serum insulin-like growth factor (IGF-I) content and IGF-I:IGF-binding protein 3 (IGFBP-3) ratio as risk factors for these same malignancies. Therefore, we sought to determine the link between COX-2 expression and the IGF axis in COX-2 gene-modified human non–small-cell lung cancer (NSCLC) cells. Overexpression of COX-2 in NSCLC cells enhanced the antiapoptotic and mitogenic effects of IGF-I and IGF-II, facilitated the autophosphorylation of the type 1 IGF receptor, increased class IA phosphatidylinositol 3′-kinase activity, and decreased expression of IGFBP-3. Thus, these findings show that COX-2 augments the stimulatory arm of the IGF axis.Keywords
This publication has 32 references indexed in Scilit:
- In vivo antitumor activity of NVP-AEW541—A novel, potent, and selective inhibitor of the IGF-IR kinaseCancer Cell, 2004
- Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumorsCancer Cell, 2004
- COX‐2‐dependent stabilization of survivin in non‐small cell lung cancerThe FASEB Journal, 2003
- Inhibition of angiotensin II activity enhanced the anti-tumor effect of cyclooxygenase-2 inhibitors Via insulin-like growth factor I receptor pathwayGastroenterology, 2003
- Cyclooxygenase-2 Inducing Mcl-1-dependent Survival Mechanism in Human Lung Adenocarcinoma CL1.0 CellsJournal of Biological Chemistry, 2001
- Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasisOncogene, 2001
- Non-small Cell Lung Cancer Cyclooxygenase-2-dependent Invasion Is Mediated by CD44Journal of Biological Chemistry, 2001
- Autophosphorylation of the Insulin-like Growth Factor I Receptor Cytoplasmic DomainBiochemical and Biophysical Research Communications, 2000
- IGF-II/IGF-I receptor pathway up-regulates COX-2 mRNA expression and PGE2 synthesis in Caco-2 human colon carcinoma cellsOncogene, 2000
- Circulating concentrations of insulin-like growth factor I and risk of breast cancerThe Lancet, 1998