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Global detection of molecular changes reveals concurrent alteration of several biological pathways in nonsmall cell lung cancer cells

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Abstract

To identify the molecular changes that occur in non-small cell lung carcinoma (NSCLC), we compared the gene expression profile of the NCI-H292 (H292) NSCLC cell line with that of normal human tracheobronchial epithelial (NHTBE) cells. The NHTBE cells were grown in a three-dimensional organotypic culture system that permits maintenance of the normal pseudostratified mucociliary phenotype characteristic of bronchial epithelium in vivo. Microarray analysis using the Affymetrix oligonucleotide chip U95Av2 revealed that 1,683 genes showed a >1.5-fold change in expression in the H292 cell line relative to the NHTBE cells. Specifically, 418 genes were downregulated and 1,265 were upregulated in the H292 cells. The expression data for selected genes were validated in several different NSCLC cell lines using quantitative real-time PCR and Western analysis. Further analysis of the differentially expressed genes indicated that WNT responses, apoptosis, cell cycle regulation and cell proliferation were significantly altered in the H292 cells. Functional analysis using fluorescence-activated cell sorting confirmed concurrent changes in the activity of these pathways in the H292 line. These findings show that (1) NSCLC cells display deregulation of the WNT, apoptosis, proliferation and cell cycle pathways, as has been found in many other types of cancer cells, and (2) that organotypically cultured NHTBE cells can be used as a reference to identify genes and pathways that are differentially expressed in tumor cells derived from bronchogenic epithelium.

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Acknowledgements

We thank Dr. Guillermina Lozano for her valuable suggestions regarding experiments and this manuscript. This work was supported by National Cancer Institute grant N01-CN-05023-39 (to L.S.), U.S. Department of Defense grant DAMD 17-02-1-0706 01 (to J.S.K.), and National Institute of Environmental Health Sciences grant 5K22-ES-000362 (to J.S.K.)

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Authors and Affiliations

  1. Section of Cancer Genetics and Microarray Core Facility, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Z. Ju, M. Kapoor & A. Ramaswamy

  2. Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    L. C. Strong

  3. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    K. Newton, K. Cheon, R. Lotan & J. S. Koo

  4. Molecular Biosciences Research Group, Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA

    Z. Ju

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  1. Z. Ju
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Correspondence to J. S. Koo.

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Communicated by G. Georgiev

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Ju, Z., Kapoor, M., Newton, K. et al. Global detection of molecular changes reveals concurrent alteration of several biological pathways in nonsmall cell lung cancer cells. Mol Genet Genomics 274, 141–154 (2005). https://doi.org/10.1007/s00438-005-0014-7

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  • DOI: https://doi.org/10.1007/s00438-005-0014-7

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