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(Chest. 2002;121:29S-30S.)
© 2002 American College of Chest Physicians

Microarray Identifies Cyclo-oxygenase-2–Dependent Modulation of Insulin-like Growth Factor Binding Protein-3 in Non-small Cell Lung Cancer Cells*

Mehis Põld, MD; M. Dohadwala, PhD, MD; J. Luo; Y. Lin, MD and S. Dubinett, MD

* From the Division of Pulmonary and Critical Care Medicine, Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA.

Correspondence to: Mehis Pold, MD, Dubinett’s Lab, Division of Pulmonary Medicine, 10833 LeComte Ave, Room 37–131, CHS, Los Angeles, CA 90095; e-mail: mpold{at}mednet.ucla.edu

Cyclo-oxygenase (COX)-2 is frequently overexpressed in non-small cell lung cancer (NSCLC). Previous studies have implicated a number of cytokines and growth factors in the regulation of COX-2 expression, and COX-2 itself modulates the expression of a variety of genes.1 2 3 4 5 Our previous studies show that prostaglandin E2, the major product of COX-2 activity, suppresses the T-cell–mediated immunity in lung cancer.6 7 In addition to its effects on cell-mediated immunity, tumor overexpression of COX-2 appears to be involved in enhanced invasion, promotion of angiogenesis, and resistance to apoptosis.8 9 10 11 Thus, there is mounting evidence indicating the importance of COX-2 in NSCLC. However, the knowledge about the changes in gene expression caused by the overexpression of COX-2 in NSCLC is fragmentary. In order to elucidate the COX-2–induced changes in NSCLC, we have conducted a microarray study using the Human Cancer Specific GeneChip (Affymetrix; Santa Clara, CA). In our study, we compared the expression of approximately 1,700 genes in the human lung adenocarcinoma cell line A549, transduced with COX-2, to A549 cells with either no or very little COX-2 expression. As a result, we have determined that the A549 cells of high COX-2 content express lower levels of insulin-like growth factor binding protein (IGFBP)-3 messenger RNA and, as determined by IGFBP-3 enzyme-linked immunosorbent assay, lower levels of free soluble IGFBP-3 protein. Thus, the amount of free soluble A549 inversely correlated with the expression level of COX-2. Previous studies have shown that IGFBP-3 antagonizes the mitogenicity of insulin-like growth factor (IGF)-1 and IGF-2.12 13 In addition, IGFBP-3 also has an IGF-independent tumor suppressor activity.14 15 16 Therefore, we hypothesize that COX-2–induced suppression of IGFBP-3 in lung cancer cells is one of the elements leading to increased tumorigenicity. This is the first study to implicate IGFBP-3 as a gene modulated by COX-2 overexpression in cancer cells.


   Footnotes
 
Abbreviations: COX = cyclo-oxgenase; IGF = insulin-like growth factor; IGFBP = insulin-like growth factor binding protein; NSCLC = non-small cell lung cancer


   References
TOP
 References
 

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