ABSTRACT
CT120, a novel membrane-associated gene implicated in lung carcinogenesis, was previously identified from chromosome 17p13.3 locus, a hot mutation spot involved in human malignancies. In the present study, we further determined that CT120 ectopic expression could promote cell proliferation activity of NIH3T3 cells using MTS assay, and monitored the downstream effects of CT120 in NIH3T3 cells with Atlas mouse cDNA expression arrays. Among 588 known genes, 133 genes were found to be upregulated or downregulated by CT120. Two major signaling pathways involved in cell proliferation, cell survival and anti-apoptosis were overexpressed and activated in response to CT120: One is the Raf/MEK/Erk signal cascades and the other is the PI3K/Akt signal cascades, suggesting that CT120 might contribute, at least in part, to the constitutively activation of Erk and Akt in human lung caner cells. In addition, some tumor metastasis associated genes cathepsin B, cathepsin D, cathepsin L, MMP-2/TIMP-2 were also upregulated by CT120, upon which CT120 might be involved in tumor invasiveness and metastasis. In addition, CT120 might play an important role in tumor progression through modulating the expression of some candidate “Lung Tumor Progression” genes including B-Raf, Rab-2, BAX, BAG-1, YB-1, and Cdc42.
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References
Parkin DM, Bray F, Ferlay J, Pisani P . Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94:153–6.
Testa JR, Liu Z, Feder M, et al. Advance in the analysis of chromosome alterations in human lung carcinomas. Cancer Genet Cytogenet 1997; 95:20–32.
Mertens F, Johansson B, Hoglund M, Mitelman F . Chromosome inbalance maps of malignant solid tumors: a cytogenetic survey of 3185 neoplasms. Cancer Res 1997; 57:2765–80.
Rodenhuis S, Slebos RJ, Boot AJ, et al. Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 1988; 48:5738–41.
Harbour JW, Lai SL, Whang-Peng J, et al. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 1988; 241:353–7.
Takahashi T, Nau MM, Chiba I, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 1989; 246:491–4.
Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994; 264:436–40.
He XH, Di YJ, Li JJ, et al. Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism. Biochem Biophys Res Commun 2002; 297:528–36.
He XH, Li JJ, Xie YH, et al. Expression of Human Novel Gene CT120 in Lung Cancer and Its Effects on Cell Growth. Ai Zheng 2003; 22:113–8 (In Chinese).
Tanaka H, Arakawa H, Yamaguchi T, et al. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 2000; 404:42–9.
Yu J, Zhang L, Hwang PM, et al. Identification and classification of p53-regulated genes. Proc Natl Acad Sci USA 1999; 96:14517–22.
Schena M, Shalon D, Davis RW, Brown PO . Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995; 270: 467–70.
Khan J, Bittner ML, Saal LH, et al. cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. Proc Natl Acad Sci USA 1999; 96:13264–9.
Mullan PB, McWilliams S, Quinn J, et al. Uncovering BRCA1-regulated signalling pathways by microarray-based expression profiling. Biochem Soc Trans 2001; 29: 678–83.
Jimenez AI, Fernandez P, Dominguez O, Dopazo A, Sanchez-Cespedes M . Growth and molecular profile of lung cancer cells expressing ectopic LKB1: down-regulation of the phospha-tidylinositol 3′-phosphate kinase/PTEN pathway. Cancer Res 2003; 63: 1382–8.
Hoshino R, Chatani Y, Yamori T, et al. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 1999; 18:813–22.
Brognard J, Dennis PA . Variable apoptotic response of NSCLC cells to inhibition of the MEK/ERK pathway by small molecules or dominant negative mutants. Cell Death Differ 2002; 9:893–904.
Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci USA 2001; 98:10983–5.
Duffy MJ . Proteases as prognostic markers in cancer. Clin Cancer Res 1996; 2:613–8.
Chapman HA, Riese RJ, Shi GP . Emerging roles for cysteine proteases in human biology. Annu Rev Physiol 1997; 59:63–88.
Krepela E, Prochazka J, Karova B, Cermak J, Roubkova H. Cysteine proteases and cysteine protease inhibitors in non-small cell lung cancer. Neoplasma 1998; 45:318–31.
Ledakis P, Tester WT, Rosenberg N, et al. Cathepsins D, B, and L in malignant human lung tissue. Clin Cancer Res 1996; 2:561–8.
Gonzalez-Avila G, Iturria C, Vadillo F, et al. 72-kD (MMP-2) and 92-kD (MMP-9) type IV collagenase production and activity in different histologic types of lung cancer cells. Pathobiology 1998; 66:5–16.
Thomas P, Khokha R, Shepherd FA, Feld R, Tsao MS . Differential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer. J Pathol 2000; 190:150–6.
Ohbayashi H . Matrix metalloproteinases in lung diseases. Curr Protein Pept Sci 2002; 3:409–21.
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We gratefully acknowledge Ms. YY ZHANG for her help in words processing. This work was supported by Major State Basic Research Development program of China (2004CB518704 and 2002CB513100).
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HE, X., LI, J., XIE, Y. et al. Altered gene expression profiles of NIH3T3 cells regulated by human lung cancer associated gene CT120. Cell Res 14, 487–496 (2004). https://doi.org/10.1038/sj.cr.7290252
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DOI: https://doi.org/10.1038/sj.cr.7290252
