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Journal of Biomedicine and Biotechnology
Volume 2009 (2009), Article ID 917084, 10 pages
Research Article

Cytotoxic Effect of Recombinant Mycobacterium tuberculosis CFP-10/ESAT-6 Protein on the Crucial Pathways of WI-38 Cells

1Institute of Biomedical Engineering, National Taiwan University, 1, Section 1, Jen-Ai Rd, Taipei 100, Taiwan
2Department of Medical Biotechnology and Laboratory Science, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan

Received 7 December 2008; Revised 3 April 2009; Accepted 29 April 2009

Academic Editor: Ying Xu

Copyright © 2009 Kun-Nan Tsai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


To unravel the cytotoxic effect of the recombinant CFP-10/ESAT-6 protein (rCFES) on WI-38 cells, an integrative analysis approach, combining time-course microarray data and annotated pathway databases, was proposed with the emphasis on identifying the potentially crucial pathways. The potentially crucial pathways were selected based on a composite criterion characterizing the average significance and topological properties of important genes. The analysis results suggested that the regulatory effect of rCFES was at least involved in cell proliferation, cell motility, cell survival, and metabolisms of WI-38 cells. The survivability of WI-38 cells, in particular, was significantly decreased to 62% with 12.5  rCFES. Furthermore, the focal adhesion pathway was identified as the potentially most-crucial pathway and 58 of 65 important genes in this pathway were downregulated by rCFES treatment. Using qRT-PCR, we have confirmed the changes in the expression levels of LAMA4, PIK3R3, BIRC3, and NFKBIA, suggesting that these proteins may play an essential role in the cytotoxic process in the rCFES-treated WI-38 cells.