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Immediate early response gene 5 in cervical cancer tissues:radiosensitivity and clinical significance
Liu Yang,Wu Yumei,Tian Ming,Zhao Hui,Yu Xinping,Zhou Pingkun
Department of Gynecological Oncology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100006,China (Liu Y,Wu YM,Tian M,Zhao H,Yu XP); Department of Radiation Toxicology and Oncology,Beijing Institute of Radiation Medicine,Beijing 100850,China (Zhou PK)
Abstract Objective To investigate the expression features of immediate early response gene 5(IER5) in patients with cervical cancer before and after radiotherapy,and to study the relationship of IER5 with radiosensitivity and clinical outcomes. Methods From 2014 to 2015,39 patients with stage Ⅱb-Ⅲb cervical cancer undergoing concurrent chemoradiotherapy were enrolled as subjects. Cervical cancer tissues were collected before and after radiotherapy with doses of 2-6,10,20,and 30 Gy. Western blotting was used to determine the relative expression of IER5 protein. Results The expression of IER5 protein in cervical cancer tissues was significantly higher after exposure to 10,20,and 30 Gy of radiation (t=3.06,4.01,6.99,P<0.01).The expression of IER5 protein was correlated with the radiation dose (r=0.511,P<0.01).There was a significant interaction between the expression of IER5 protein under different doses of irradiation and the tumor size before radiotherapy (F=3.212,P<0.05).When the tumor diameter was<4 or 4-5 cm before treatment,the expression of IER5 had significant radiation dose-dependent variation (F=10.493,P<0.01;F=9.977,P<0.01).However,there was no significant dose-dependent variation in the expression of IER5 protein when the tumor diameter was>5 cm. Conclusions The expression of IER5 protein in patients with cervical cancer is significantly higher after radiotherapy. Moreover,IER5 expression gets higher with the increase in radiation dose,indicating that IER5 is related to the radiosensitivity of patients with cervical cancer. The smaller the tumor,the more radiation dose-dependent the IER5 expression.
Liu Yang,Wu Yumei,Tian Ming et al. Immediate early response gene 5 in cervical cancer tissues:radiosensitivity and clinical significance[J]. Chinese Journal of Radiation Oncology, 2016, 25(12): 1345-1349.
Liu Yang,Wu Yumei,Tian Ming et al. Immediate early response gene 5 in cervical cancer tissues:radiosensitivity and clinical significance[J]. Chinese Journal of Radiation Oncology, 2016, 25(12): 1345-1349.
[1] Meng XY,Liao Y,Liu XP et al. Concurrent cisplatin-based chemoradiotherapy versus exclusive radiotherapy in high-risk cervical cancer:a meta-analysis[J].Onco Targets Ther,2016,9:1875-88.10.2147/OTT.S97436. [2] Luo YM,Xia NX,Yang L,et al. CTC1 increases the radioresistance of human melanoma cells by inhibiting telomere shortening and apoptosis[J].Int J Mol Med,2014,33(6):1484-1490.10.3892/ijmm.2014.1721. [3] Zhao J,Liu K,Lu J,et al. Alternariol induces DNA polymerase β expression through the PKA-CREB signaling pathway[J].Int J Oncol,2012,40(6):1923-1928.10.3892/ijo.2012.1398. [4] Ding KK,Shang ZF,Hao C,et al. Induced expression of the IER5 gene by gamma-ray irradiation and its involvement in cell cycle checkpoint control and survival[J].Radiat Environ Biophys,2009,48(2):205-213.10.1007/s00411-009-0213-4. [5] Nakamura S,Nagata Y,Tan L,et al. Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of leukemic progenitor cells through NF-YB and p300 in acute myeloid leukemia[J/OL].PLoS One,2011,6(11):e28011.10.1371/journal.pone.0028011. [6] Yang C,Wang Y,Hao C,et al. IER5 promotes irradiation-and cisplatin-induced apoptosis in human hepatocellular carcinoma cells[J].Am J Transl Res,2016,8(4):1789-1798.PMID:27186303. [7] Fujiyoshi N,Ushijima K,Kawano K,et al. Radiation effects on DNA content of cervical cancer cells:A rapid evaluation of radiation sensitivity by laser scanning cytometry[J].Mol Clin Oncol,2015,3(1):51-54.10.3892/mco.2014.413. [8] 崔巍,尹玲玲,董凌月,等.早期反应基因Ier5启动子区放射敏感的转录因子结合位点研究[J].中华放射医学与防护杂志,2012,32(1):15-19.10.3760/cma.j.issn.0254-5098.2012.01.004. Cui W,Yin LL,Dong LY,et al. Binding sites of transcription factor binding sites in the Ier5 promoter region of early response genes[J].Chin J Radiol Med Prect,2012,32(1):15-19.10.3760/cma.j.issn.0254-5098.2012.01.004. [9] 丁库克,沈晶晶,许莉莉,等.γ射线照射对IER5基因mRNA表达的影响[J].中华放射医学与防护杂志,2008,28(1):5-8.10.3760/cma.j.issn.0254-5098.2008.01.002. Ding KK.Shen JJ,Xu LL,et al. Effect of gamma ray irradiation on the expression of mRNA gene in IER5 gene[J].Chin J Radiol Med Prect,2008,28(1):5-8.10.3760/cma.j.issn.0254-5098.2008.01.002. [10] Shi HM,Ding KK,Zhou PK,et al. Radiation-induced expression of is dose-dependent and not associated with the clinical outcomes of radiotherapy in cervical cancer[J].Oncol Lett,2016,11(2):1309-1314.10.3892/ol.2016.4086. [11] Mizuno H,Kitada K,Nakai K,et al. PrognoScan:a new database for meta-analysis of the prognostic value of genes[J].BioMed Central Ltd,2009,2:18.10.1186/1755-8794-2-18. [12] Ishikawa Y,Sakurai H.Heat-induced expression of the immediate-early gene IER5 and its involvement in the proliferation of heat-shocked cells[J].FEBS J,2015,282(2):332-340.10.1111/febs.13134. [13] Asano Y,Kawase T,Okabe A,et al. IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis[J].Sci Rep,2016,6:19174.10.1038/srep19174. [14] Mendillo ML,Santagata S,Koeva M,et al. HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers[J].Cell,2012,150(3):549-62.10.1016/j.cell.2012.06.031. [15] Hirakawa M,Nagai Y,Toita T,et al.High-risk group for locoregional recurrence in patients with stage ⅠB-ⅡB squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy[J].Anticancer Res,2011,31(4):1437-1441.PMID:21508399. [16] Kudaka W,Nagai Y,Toita T,et al. Long-term results and prognostic factors in patients with stage Ⅲ-IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study[J].Int J Clin Oncol,2013,18(5):916-921.10.1007/s10147-012-0457-x.