Department of Radiation Oncology,Anhui Provincial Hospital,Anhui Medical University,Hefei 230001,China (Zhou LR,Bai L,Qain LT);Laboratory of Molecule Cancer,Anhui Provincial Tumor Hospital,Anhui Medical University,Hefei 230001,China (Wang L,Cheng M)
AbstractObjective To establish a radioresistant esophageal squamous cancer cell line, and to identify the radioresistant genes and mechanisms. Methods The radioresistant KYSE410-res cell line was established by repeated exposure of cell line KYSE410 to radiation. The proliferation and apoptosis of esophageal squamous cancer cells were evaluated before and after radiation. The changes in gene expression of the esophageal squamous cancer cells after radiation were determined by gene microarray and analyzed by group t test. The genes with significant difference in expression after radiation were validated. Results The KYSE410-res cells had significantly enhanced proliferation and anti-apoptosis than the KYSE410 cells (all P<0.05). The result of gene microarray showed that compared with the KYSE410 cells, the KYSE410-res cells had the expression of 463 and 251 genes upregulated and downregulated by no less than 4 folds, respectively. Those genes with different expression levels after radiation were mainly responsible for cell proliferation, adhesion, signal transduction, angiogenesis, reactive oxygen metabolism, cell damage repair, and the MAPK/ERK signaling pathway. OAS2 and UBD were key proteins in the network. In the KYSE410-res cells, the expression of HLA-DQB1, MMP1, NCAM1, ZNF521, GPC6, SELENBP1, LCN15, and TFPI-2 genes measured by real-time PCR was consistent with that measured by gene microarray. Conclusions Abnormal activation of the MAPK/ERK signaling pathway, upregulated expression of OAS2 and UBD, downregulated expression of TFPI-2, and upregulated expression of MMPs may play a role in radioresistance of esophageal cancer cells.
Zhou Lingran,Bai Lu,Wang Liang et al. Gene expression profiling of a radioresistant esophageal squamous cancer cell line[J]. Chinese Journal of Radiation Oncology, 2017, 26(2): 215-221.
Zhou Lingran,Bai Lu,Wang Liang et al. Gene expression profiling of a radioresistant esophageal squamous cancer cell line[J]. Chinese Journal of Radiation Oncology, 2017, 26(2): 215-221.
[1] Chen WQ,Zheng RS,Baade PD,et al. Cancer statistics in china,2015[J].CA Cancer J Clin,2016,66(2):115-132.DOI:10.3322/caac.21338. [2] Ariga H,Nemoto K,Miyazaki S,et al. Prospective comparison of surgery alone and chemoradiotherapy with selective surgery in resectable squamous cell carcinoma of the esophagus[J].Int J Radiat Oncol Biol Phys,2009,75(2):348-356.DOI:10.1016/j.ijrobp.2009.02.086. [3] Chiu PWY,Chan ACW,Leung SF,et al. Multicenter prospective randomized trial comparing standard esophagectomy with chemoradiotherapy for treatment of squamous esophageal cancer:early results from the chinese university research group for esophageal cancer (cure)[J].J Gastrointest Surg,2005,9(6):794-802.DOI:10.1016/j.gassur.2005.05.005. [4] Bansal N,Mims J,Kuremsky JG,et al. Broad phenotypic changes associated with gain of radiation resistance in head and neck squamous cell cancer[J].Antioxid Redox Signal,2014,21(2):221-236.DOI:10.1089/ars.2013.5690. [5] Lin HY,Hung SK,Lee MS,et al. DNA methylome analysis identifies epigenetic silencing of fhit as a determining factor for radiosensitivity in oral cancer:an outcome-predicting and treatment-implicating study[J].Oncotarget,2015,6(2):915-934.DOI:10.18632/oncotarget.2821. [6] Lin HY,Huang THM,Chan MWY.Aberrant epigenetic modifications in radiation-resistant head and neck cancers[A]//Verma M.Cancer epigenetics:methods in molecular biology[M].New York:Springer,2015,1238:321-332.DOI:10.1007/978-1-4939-1804-1_17. [7] Yang LH,Han Y,Li G,et al. Axin gene methylation status correlates with radiosensitivity of lung cancer cells[J].BMC Cancer,2013,13:368.DOI:10.1186/1471-2407-13-368. [8] NCCN. org. Nccn clinical practice guidelines in oncology:esophageal and esophagogastric junction cancers[Z].NCCN Guidelines,2016. [9] Kelley K,Knisely J,Symons M,et al. Radioresistance of brain tumors[J].Cancers,2016,8(4):E42.DOI:10.3390/cancers8040042. [10] Munshi A,Ramesh R.Mitogen-activated protein kinases and their role in radiation response[J].Genes Cancer,2013,4(9-10):401-408.DOI:10.1177/1947601913485414. [11] Hein AL,Ouellette MM,Yan Y.Radiation-induced signaling pathways that promote cancer cell survival (review)[J].Int J Oncol,2014,45(5):1813-1819.DOI:10.3892/ijo.2014.2614. [12] Yacoub A,McKinstry R,Hinman D,et al. Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling[J].Radiat Res,2003,159(4):439-452.DOI:10.1667/0033-7587(2003)159[0439:EGFAIR]2.0.CO;2 [13] Zhu B,Zhang P,Zeng P,et al. Tissue factor pathway inhibitor-2 silencing promotes hepatocellular carcinoma cell invasion in vitro[J].Anat Rec,2013,296(11):1708-1716.DOI:10.1002/ar.22789. [14] Lavergne M,Jourdan ML,Blechet C,et al. Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer[J].FEBS Open Bio,2013,3(1):291-301.DOI:10.1016/j.fob.2013.06.004. [15] Wang GJ,Wang YB,Li DN,et al. Expression of tissue factor pathway inhibitor-2 in gastric stromal tumor and its clinical significance[J].Exp Ther Med,2014,7(2):513-517.DOI:10.3892/etm.2013.1448. [16] Ran YL,Pan J,Hu H,et al. A novel role for tissue factor pathway inhibitor-2 in the therapy of human esophageal carcinoma[J].Human Gene Therapy,2009,20(1):41-49.DOI:10.1089/hum.2008.129. [17] George J,Gondi CS,Dinh DH,et al. Restoration of tissue factor pathway inhibitor-2 in a human glioblastoma cell line triggers caspase mediated pathway and apoptosis[J].Clin Cancer Res,2007,13(12):3507-3517.DOI:10.1158/1078-0432.CCR-06-3023. [18] Radisky ES,Radisky DC.Matrix metalloproteinases as breast cancer drivers and therapeutic targets[J].Front Biosci,2015,20:1144-1163. [19] Dar AA,Pradhan TN,Kulkarni DP,et al. Extracellular 2′5′-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer[J].Immunology,2016,147(2):251-264.DOI:10.1111/imm.12560. [20] Basler M,Buerger S,Groettrup M.The ubiquitin-like modifier FAT10 in antigen processing and antimicrobial defense[J].Mol Immunol,2015,68(2):129-132.DOI:10.1016/j.molimm.2015.04.012. [21] Lee CGL,Ren JW,Cheong ISY,et al. Expression of the FAT10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers[J].Oncogene,2003,22(17):2592-2603.DOI:10.1038/sj.onc.1206337. [22] Choi Y,Kim JK,Yoo JY.NfκB and STAT3 synergistically activate the expression of FAT10,a gene counteracting the tumor suppressor p53[J].Mol Oncol,2014,8(3):642-655.DOI:10.1016/j.molonc.2014.01.007. [23] Ren JW,Wang Y,Gao Y,et al. FAT10 mediates the effect of TNF-α in inducing chromosomal instability[J].J Cell Sci,2011,124(21):3665-3675.DOI:10.1242/jcs.087403.
2017, Vol. 26 
