Oral cancer overexpressed 1 (ORAOV1): A regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma
Lu Jiang
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
The first two authors contributed equally to this paper.
Search for more papers by this authorXin Zeng
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
The first two authors contributed equally to this paper.
Search for more papers by this authorHanshuo Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorZhi Wang
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorJun Shen
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorJingping Bai
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorYuanyuan Zhang
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorFeng Gao
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorMin Zhou
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorCorresponding Author
Qianming Chen
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Fax: +86-28-85405251
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, ChinaSearch for more papers by this authorLu Jiang
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
The first two authors contributed equally to this paper.
Search for more papers by this authorXin Zeng
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
The first two authors contributed equally to this paper.
Search for more papers by this authorHanshuo Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorZhi Wang
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorJun Shen
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorJingping Bai
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorYuanyuan Zhang
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorFeng Gao
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorMin Zhou
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Search for more papers by this authorCorresponding Author
Qianming Chen
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China
Fax: +86-28-85405251
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, ChinaSearch for more papers by this authorAbstract
Oral Cancer Overexpressed 1 (ORAOV1) is a novel gene locating at chromosome band 11q13. Recent studies have suggested its role as a candidate oncogene in oral squamous cell carcinoma (OSCC) and its prognostic value for patients with OSCC. Till now, the detailed function of ORAOV1 in OSCC has remained undefined. In this study, we have investigated the role of ORAOV1 in OSCC tumorigenesis by down-regulating its expression. Small interfering RNA (siRNA) has been applied to inhibit the expression of ORAOV1 in OSCC cells. We found that the OSCC cells with reduced ORAOV1 showed retarded cell growth in vitro and displayed inhibition in both tumor growth and tumor angiogenesis in vivo. Further analyses reveal that the retarded cell growth is associated with an increase in apoptosis involving the activation of caspase 3-dependent pathway and a cell cycle arrest at the S-phase with a downregulation of cyclin A, cyclin B1 and cdc2. The suppressed tumor growth in vivo may be attributed to synergistic effect between inhibition in cell growth and suppression of tumor angiogenesis. The latter is most likely because of a suppression of VEGF. Taken together, we demonstrate that ORAOV1 plays pivotal roles in the growth and angiogenesis of OSCC. Thus, ORAOV1 may be a novel target that could be explored to develop therapeutic strategy in OSCC management. © 2008 Wiley-Liss, Inc.
References
- 1 Neville BW,Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin 2002; 52: 195–215.
- 2
Lewin F,Norell SE,Johansson H,Gustavsson P,Wennerberg J,Biorklund A,Rutqvist LE.
Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck.
Cancer
1998;
82:
1367–75.
10.1002/(SICI)1097-0142(19980401)82:7<1367::AID-CNCR21>3.0.CO;2-3 CAS PubMed Web of Science® Google Scholar
- 3 Scully C. Oral squamous cell carcinoma: from a hypothesis about a virus to concern about possible sexual transmission. Oral Oncol 2002; 38: 227–34.
- 4
Schwab M.
Amplification of oncogenes in human cancer cells.
Bio Essays
1998;
20:
473–9.
10.1002/(SICI)1521-1878(199806)20:6<473::AID-BIES5>3.0.CO;2-N CAS PubMed Web of Science® Google Scholar
- 5 Huang X,Gollin SM,Raja S,Godfrey TE. High-resolution mapping of the 11q13 amplicon and identification of a gene. TAOS1, that is amplified and overexpressed in oral cancer cells. Proc Natl Acad Sci USA 2002; 99: 11369–74.
- 6 Xia J,Chen QM,Li BQ,Zeng X. Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with clinicopathological features. Oral Oncol 2007; 43: 508–14.
- 7 Shen J,Huang CH,Jiang L,Gao F,Wang Z,Zhang YY,Bai JP,Zhou HM,Chen QM. Enhancement of cisplatin induced apoptosis by suberoylanilide hydroxamic acid in human oral squamous cell carcinoma cell lines. Biochem Pharmacol 2007; 73: 1901–9.
- 8 Gioanni J,Fischel JL,Lambert JC,Demard F,Mazeau C,Zanghellini E,Ettore F,Formento P,Chauvel P,Lalanne CM. Two new human tumor cell lines derived from squamous cell carcinomas of the tongue: establishment, characterization and response to cytotoxic treatment. Eur J Cancer Clin Oncol 1988; 24: 1445–55.
- 9 Liu J,Prolla G,Rostagno A,Chiarle R,Feiner H,Inghirami G. Initiation of translation from a downstream in-frame AUG codon on BRCA1 can generate the novel isoform protein DBRCA1 (17aa). Oncogene 2000; 19: 2767–73.
- 10 Weidner N. Intratumoral microvessel density as a prognostic factor in cancer. Am J Pathol 1995; 147: 9–19.
- 11 Park JW,Choi YJ,Jang MA,Lee YS,Jun DY,Suh SI,Baek WK,Suh MH,Jin IN,Kwon TK. Chemopreventive agent resveratrol, a natural product derived from grapes, reversibly inhibits progression through S and G2 phases of the cell cycle in U937 cells. Cancer Lett 2001; 163: 43–9.
- 12 Tschaharganeh D,Ehemann V,Nussbaum T,Schirmacher P,Breuhahn K. Non-specific effects of siRNAs on tumor cells with implications on therapeutic applicability using RNA interference. Pathol Oncol Res 2007; 13: 84–90.
- 13 Zhang H,Gavin M,Dahiya A,Postigo A,Ma D,Luo R,Harbour J,Dean D. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 2000; 101: 79–89.
- 14 Xie S,Xie B,Lee MY,Dai W. Regulation of cell cycle checkpoints by polo-like kinases. Oncogene 2005; 24: 277–86.
- 15 Chan TA,Hwang PM,Hermeking H,Kinzler KW,Vogelstein B. Cooperative effects of genes controlling the G2/M checkpoint. Gene Dev 2000; 14: 1584–8.
- 16 Stucki M,Stagljar I,Jonsson ZO,Hubscher U. A coordinated interplay: proteins with multiple functions in DNA replication. DNA repair, cell cycle/checkpoint control, and transcription. Prog Nucleic Acids Res Mol Biol 2001; 65: 261–98.
- 17 Maga G,Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 2003; 116: 3051–60.
- 18 Podar K,Anderson KC. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood 2005; 105: 1383–95.
- 19 Carmeliet P,Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249–57.
- 20 Yancopoulos GD,Davis S,Gale NW,Rudge JS,Wiegand SJ,Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000; 407: 242–8.
- 21 Liang AB,Gu LJ. Higher expression of cytochrome-c and caspase-3 in the primary acute lymphoblastic leukemic cells with negative expression of VEGF and its receptors than with positive expressed cells under VP16 induction. Blood 2004; 104: abstract 4448.
- 22 Jin K,Mao XO,Batteur SP,McEachron E,Leahy A,Greenberg DA. Caspase-3 and the regulation of hypoxic neuronal death by vascular endothelial growth factor. Neuroscience 2001; 108: 351–8.
- 23 Volm M,Mattern J,Koomagi R. Inverse correlation between apoptotic (Fas ligand, caspase-3) and angiogenic factors (VEGF, microvessel density) in squamous cell lung carcinomas. Anticancer Res 1999; 19: 1669–71.
- 24 Holen T,Amarzguioui M,Wiiger MT,Babaie E,Prydz H. Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nucleic Acids Res 2002; 30: 1757–66.
- 25 Amarzguioui M,Peng Q,Wiiger MT,Vasovic V,Babaie E,Holen T,Nesland JM,Prydz H. Ex vivo and in vivo delivery of anti-tissue factor short interfering RNA inhibits mouse pulmonary metastasis of B16 melanoma cells. Clin Cancer Res 2006; 12: 4055–61.
- 26 Takei Y,Kadomatsu K,Yuzawa Y,Matsuo S,Muramatsu T. A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics. Cancer Res 2004; 64: 3365–70.
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