Cytotoxic effect of recombinant mycobacterium tuberculosis CFP-10/ESAT-6 protein on the crucial pathways of WI-38 cells
Journal
Journal of Biomedicine and Biotechnology
Journal Volume
2009
Pages
-
Date Issued
2009
Author(s)
Abstract
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 M 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. ? 2009 Kun-Nan Tsai et al.
SDGs
Other Subjects
baculoviral IAP repeat containing 3; complementary RNA; culture filtrate protein 10; early secretory antigenic target 6; integrin; laminin alpha4; phosphatidylinositol 3 kinase; protein kinase B; recombinant protein; RNA; unclassified drug; bacterial protein; BIRC3 protein, human; CFP 10 protein, Mycobacterium tuberculosis; CFP-10 protein, Mycobacterium tuberculosis; I kappa B; inhibitor of apoptosis protein; LAMA4 protein, human; laminin; NF kappaB inhibitor alpha; NF-kappaB inhibitor alpha; recombinant protein; amino acid metabolism; article; biosynthesis; cell metabolism; cell motility; cell proliferation; cell survival; cytotoxicity; enzyme activity; Escherichia coli; gene expression regulation; human; human cell; lung fibroblast; microarray analysis; Mycobacterium tuberculosis; nonhuman; polyacrylamide gel electrophoresis; protein protein interaction; reverse transcription polymerase chain reaction; signal transduction; cell line; DNA microarray; drug effect; fibroblast; genetics; metabolism; reproducibility; Mycobacterium tuberculosis; Bacterial Proteins; Cell Line; Cell Survival; Fibroblasts; Humans; I-kappa B Proteins; Inhibitor of Apoptosis Proteins; Laminin; Oligonucleotide Array Sequence Analysis; Recombinant Proteins; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction
Type
journal article