Cytotoxic Effect of RecombinantMycobacterium tuberculosisCFP-10/ESAT-6 Protein on the Crucial Pathways of WI-38 Cells

Kun-Nan Tsai, Err-Cheng Chan, Tsung-Yeh Tsai, Kuei-Tien Chen, Chun-Yu Chen, Kenneth Hung, Chung-Ming Chen
2009 Journal of Biomedicine and Biotechnology  
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
more » ... fect 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 μMrCFES. 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.
doi:10.1155/2009/917084 pmid:19584916 pmcid:PMC2702506 fatcat:tuugq4mui5hmfh6um4yskr7y6a