A total of 437 human full-length cDNAs isolated by microarray analysis of liver and/or gastric cancer tissues were evaluated for their relevance to cancer using the fission yeast Schizosaccharomyces pombe. Overexpression of 161 human cDNAs in S. pombe caused growth inhibition and/or morphological changes, which can be considered as cancer-related phenotypes of S. pombe. Sixteen genes causing growth defects and morphological changes at the same time were chosen to validate their ostensible oncogenic properties. They were highly expressed in liver and/or gastric cancer cell lines. Also, when the mouse embryonic fibroblast cell type NIH3T3 was transfected with these genes, the proliferation rates of cells were increased by 32% to 120%. This study demonstrates that fission yeast can be used as an advantageous and powerful tool for the rapid screening of human genes relevant to cancer. Furthermore, the human genes screened can be tested further as diagnostic markers and potential therapeutic targets for liver and stomach cancers. They also can be studied further for the elucidation of mechanisms involved in carcinogenesis. (Journal of Biomolecular Screening 2007:568-577)
Brugge JS, Jarosik G., Andersen J., Queral-Lustig A., Fedor-Chaiken M., Broach JR: Expression of Rous sarcoma virus transforming protein pp60v-src in Saccharomyces cerevisiae cells. Mol Cell Biol1987;7(6): 2180-2187.
2.
Boschelli F. : Expression of p60v-src in Saccharomyces cerevisiae results in elevation of p34CDC28 kinase activity and release of the dependence of DNA replication on mitosis. Mol Cell Biol1994;14(9):6409.
3.
Nigro JM, Sikorski R., Reed SI, Vogelstein B.: Human p53 and CDC2Hs genes combine to inhibit the proliferation of Saccharomyces cerevisiae. Mol Cell Biol1992 ;12(3):1357-1365.
4.
Tugendreich S., Perkins E., Couto J., Barthmaier P., Sun D., Tang S., et al: A streamlined process to phenotypically profile heterologous cDNAs in parallel using yeast cell-based assays. Genome Res2001;11(11):1899-1912.
5.
Russell P., Nurse P.: Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell1987;49(4):559-567.
6.
Jang Y-J., Kil Y-S., Ahn J-H., Ji J-H., Lim J-S., Won M., et al: Overexpression phenotypes of Plk1 and Ndrg2 in Schizosaccharomyces pombe: fission yeast system for mammalian gene study. Key Eng Mater2005;277:1-6.
7.
Won M., Park SK, Hoe KL, Jang YJ, Chung KS, Kim DU, et al: Rkp1/Cpc2, a fission yeast RACK1 homolog, is involved in actin cytoskeleton organization through protein kinase C, Pck2, signaling. Biochem Biophys Res Commun2001;282(1):10-15.
8.
Chung KS, Won M., Lee SB, Jang YJ, Hoe KL, Kim DU, et al: Isolation of a novel gene from Schizosaccharomyces pombe: stm1+ encoding a seven-transmembrane loop protein that may couple with the heterotrimeric Galpha 2 protein, Gpa2. J Biol Chem2001;276(43):40190-40201.
9.
Jang YJ, Won M., Chung KS, Kim DU, Hoe KL, Park C., et al: A novel protein, Psp1, essential for cell cycle progression of Schizosaccharomyces pombe is phosphorylated by Cdc2-Cdc13 upon entry into G0-like stationary phase of cell growth. J Biol Chem1997;272(32):19993-20002.
10.
Ink B., Zornig M., Baum B., Hajibagheri N., James C., Chittenden T., et al: Human Bak induces cell death in Schizosaccharomyces pombe with morphological changes similar to those with apoptosis in mammalian cells. Mol Cell Biol1997;17(5):2468-2474.
11.
Lee MG, Nurse P.: Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature1987;327(6117):31-35.
12.
Nagata A., Igarashi M., Jinno S., Suto K., Okayama H.: An additional homolog of the fission yeast cdc25+ gene occurs in humans and is highly expressed in some cancer cells. New Biol1991;3(10):959-968.
13.
Igarashi M. , Nagata A., Jinno S., Suto K., Okayama H.: Wee1(+)-like gene in human cells. Nature1991;353(6339):80-83.
14.
Draetta G., Brizuela L., Potashkin J., Beach D.: Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+. Cell1987;50(2):319-325.
15.
Ichijo H., Nishida E., Irie K., ten Dijke P., Saitoh M., Moriguchi T., et al: Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science1997;275(5296):90-94.
16.
Forsburg SL , Nurse P.: Identification of a G1-type cyclin puc1+ in the fission yeast Schizosaccharomyces pombe. Nature1991;351(6323):245-248.
17.
Fikes JD, Becker DM, Winston F., Guarente L.: Striking conservation of TFIID in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Nature1990;346(6281):291-294.
18.
Bischoff JR , Casso D., Beach D.: Human p53 inhibits growth in Schizosaccharomyces pombe. Mol Cell Biol1992;12(4):1405-1411.
19.
Zhang C., Rasmussen C., Chang LJ: Cell cycle inhibitory effects of HIV and SIV Vpr and Vpx in the yeast Schizosaccharomyces pombe. Virology1997;230(1):103-112.
20.
Ryser S., Vial E., Magnenat E., Schlegel W., Maundrell K.: Reconstitution of caspase-mediated cell-death signalling in Schizosaccharomyces pombe. Curr Genet1999;36(1-2):21-28.
21.
Kim NS, Hahn Y., Oh JH, Lee JY, Oh KJ, Kim JM, et al: Gene cataloging and expression profiling in human gastric cancer cells by expressed sequence tags. Genomics2004;83(6):1024-1045.
22.
Kim B., Bang S., Lee S., Kim S., Jung Y., Lee C., et al: Expression profiling and subtype-specific expression of stomach cancer. Cancer Res2003;63(23): 8248-8255.
23.
Choi JK, Choi JY, Kim DG, Choi DW, Kim BY, Lee KH, et al: Integrative analysis of multiple gene expression profiles applied to liver cancer study. FEBS Lett2004;565(1-3):93-100.
24.
Ha GH, Lee SU, Kang DG, Ha NY, Kim SH, Kim J., et al: Proteome analysis of human stomach tissue: separation of soluble proteins by two-dimensional polyacrylamide gel electrophoresis and identification by mass spectrometry. Electrophoresis2002 ;23(15):2513-2524.
25.
Kim J., Kim SH, Lee SU, Ha GH, Kang DG, Ha NY, et al: Proteome analysis of human liver tumor tissue by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of disease-related proteins. Electrophoresis2002;23(24):4142-4156.
26.
Moreno S., Klar A., Nurse P.: Molecular genetic analysis of fission yeast Schizosaccharomyces pombe . Methods Enzymol1991;194:795-823.
27.
Forsburg SL , Sherman DA: General purpose tagging vectors for fission yeast. Gene1997;191(2):191-195.
28.
Marques ET Jr, Chikhlikar P., de Arruda LB, Leao IC, Lu Y., Wong J., et al: HIV-1 p55Gag encoded in the lysosome-associated membrane protein-1 as a DNA plasmid vaccine chimera is highly expressed, traffics to the major histocompatibility class II compartment, and elicits enhanced immune responses. J Biol Chem2003;278(39):37926-37936.
29.
Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, et al: Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells . Clin Cancer Res2005;11(2 Pt 1):473-482.
30.
Maundrell K. : nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine. J Biol Chem1990;265(19):10857-10864.
31.
Pan Y., Bi F., Liu N., Xue Y., Yao X., Zheng Y., et al: Expression of seven main Rho family members in gastric carcinoma . Biochem Biophys Res Commun2004;315(3):686-691.
32.
Lakka SS, Gondi CS, Yanamandra N., Olivero WC, Dinh DH, Gujrati M., et al: Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene2004;23(27):4681-4689.
33.
Teymoortash A., Pientka A., Schrader C., Tiemann M., Werner JA: Expression of galectin-3 in adenoid cystic carcinoma of the head and neck and its relationship with distant metastasis . J Cancer Res Clin Oncol2005;132(1):1-6.
34.
Ushigome M. , Ubagai T., Fukuda H., Tsuchiya N., Sugimura T., Takatsuka J., et al: Up-regulation of hnRNP A1 gene in sporadic human colorectal cancers. Int J Oncol2005;26(3):635-640.
35.
Brantley-Sieders DM, Chen J.: Eph receptor tyrosine kinases in angiogenesis: from development to disease. Angiogenesis2004;7(1):17-28.
36.
Berti C., Fontanella B., Ferrentino R., Meroni G.: Mig12, a novel Opitz syndrome gene product partner, is expressed in the embryonic ventral midline and co-operates with Mid1 to bundle and stabilize microtubules. BMCCell Biol2004;5:9.
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