This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taxman, D. J. Articles by Ting, J. P-Y. Search for Related Content PubMed PubMed Citation Articles by Taxman, D. J. Articles by Ting, J. P-Y.

Transcriptional Profiling of Targets for Combination Therapy of Lung Carcinoma with Paclitaxel and Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase Inhibitor¹

Lineberger Comprehensive Cancer Center [D. J. T., J. P. M., C. C., D. T. B., J. P-Y. T.], Department of Microbiology and Immunology [J. P. M., C. C., J. P-Y. T.], and Curriculum in Genetics and Molecular Biology [D. T. B., J. P-Y. T.], University of North Carolina at Chapel Hill, North Carolina 27599-7295

A combination of paclitaxel (Taxol) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK/Erk) inhibitor represents a rational new approach to chemotherapy. We performed Affymetrix microarray analysis to understand the global effects of this combination in lung carcinoma. Genes involved in cell cycle control, apoptosis, adhesion, proliferation, invasion, and metastasis were modulated. We observed similar patterns of gene modulation in ovarian and melanoma cell lines, indicating the general applicability of these findings. Functional genomic analysis identified two genes as new targets of drug-induced tumor apoptosis. The MGSA/Gro1 gene, important in melanoma growth, was induced by paclitaxel and reduced by MEK inhibition. Blockage of paclitaxel-induced melanoma growth stimulatory activity significantly reduced melanoma growth. Additionally, the expression of topoisomerase IIIß, which exhibited a clear pattern of gene reduction by a combination of the two drugs, was significantly increased (5.7-fold) in primary lung cancers but not adjacent tissues. These findings provide potential new biomarkers and gene targets for the development of improved cancer treatment.

This article has been cited by other articles:

				H. Hu, G.-x. Li, L. Wang, J. Watts, G. F. Combs Jr., and J. Lu Methylseleninic Acid Enhances Taxane Drug Efficacy against Human Prostate Cancer and Down-Regulates Antiapoptotic Proteins Bcl-XL and Survivin Clin. Cancer Res., February 15, 2008; 14(4): 1150 - 1158. [Abstract] [Full Text] [PDF]

				U. Vijapurkar, W. Wang, and R. Herbst Potentiation of Kinesin Spindle Protein Inhibitor-Induced Cell Death by Modulation of Mitochondrial and Death Receptor Apoptotic Pathways Cancer Res., January 1, 2007; 67(1): 237 - 245. [Abstract] [Full Text] [PDF]

				M. Moscova, D. J. Marsh, and R. C. Baxter Protein Chip Discovery of Secreted Proteins Regulated by the Phosphatidylinositol 3-Kinase Pathway in Ovarian Cancer Cell Lines Cancer Res., February 1, 2006; 66(3): 1376 - 1383. [Abstract] [Full Text] [PDF]

				H. Hu, C. Jiang, C. Ip, Y. M. Rustum, and J. Lu Methylseleninic Acid Potentiates Apoptosis Induced by Chemotherapeutic Drugs in Androgen-Independent Prostate Cancer Cells Clin. Cancer Res., March 15, 2005; 11(6): 2379 - 2388. [Abstract] [Full Text] [PDF]

				G.-C. Huang, S.-Y. Liu, M.-H. Lin, Y.-Y. Kuo, and Y.-C. Liu The Synergistic Cytotoxicity of Cisplatin and Taxol in Killing Oral Squamous Cell Carcinoma Jpn. J. Clin. Oncol., September 1, 2004; 34(9): 499 - 504. [Abstract] [Full Text] [PDF]

				J. A. Whitsett, C. J. Bachurski, K. C. Barnes, P. A. Bunn Jr., L. M. Case, D. N. Cook, D. Crooks, M. W. Duncan, L. Dwyer-Nield, R. C. Elston, et al. Functional Genomics of Lung Disease Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2/S1): S1 - S81. [Full Text] [PDF]

				X. Lu, W. E. Burgan, M. A. Cerra, E. Y. Chuang, M.-H. Tsai, P. J. Tofilon, and K. Camphausen Transcriptional signature of flavopiridol-induced tumor cell death Mol. Cancer Ther., July 1, 2004; 3(7): 861 - 872. [Abstract] [Full Text] [PDF]