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Altered Gene Expression Profiles Define Pathways in Colorectal Cancer Cell Lines Affected by Celecoxib

¹ Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland; ² Basic Research Program, ³ Advanced Biomedical Computing Center, and ⁴ Laboratory of Molecular Technology, Science Applications International Corporation, Inc., Frederick, Maryland; and ⁵ Panjwani Center for Molecular Medicine, University of Karachi, Karachi, Pakistan

Requests for reprints: Iqbal U. Ali, Molecular Oncology Program, Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Phone: 92-21-763-0801; Fax: 92-21-481-9018-9. E-mail: iuali{at}cyber.net.pk

It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2–independent activities. In an attempt to better understand COX-2–independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2–positive and COX-2–deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3051–61)

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				N. FATIMA, D. CHELIUS, B. T. LUKE, M. YI, T. ZHANG, S. STAUFFER, R. STEPHENS, P. LYNCH, K. MILLER, T. GUSZCZYNSKI, et al. Label-free Global Serum Proteomic Profiling Reveals Novel Celecoxib-modulated Proteins in Familial Adenomatous Polyposis Patients Cancer Genomics Proteomics, January 1, 2009; 6(1): 41 - 49. [Abstract] [Full Text] [PDF]