ATF5在复发鼻咽癌组织中的表达及意义
|
摘要
目的观察复发鼻咽癌组织ATF5(Activating transcription factor 5,ATF5)蛋白表达变化情况,探讨ATF5表达水平与复发鼻咽癌的相关性及可能机制。方法采用免疫组织化学法比较6例同一初发和复发鼻咽癌组织及鼻咽正常组织中ATF5蛋白的表达水平,免疫细胞化学法、细胞免疫荧光法检测不同剂量的X线对鼻咽癌HONE-1细胞ATF5蛋白表达水平的影响。结果 ATF5蛋白在鼻咽癌组织中表达水平显著高于鼻咽正常组织(P均<0.05),亚细胞主要定位于细胞浆;局部复发鼻咽癌组织ATF5蛋白表达水平显著高于初发鼻咽癌组织(P<0.05),且亚细胞主要定位于细胞核;X线(30Gy、40Gy、50Gy)能促进鼻咽癌HONE-1细胞ATF5蛋白水平显著上调(P均<0.05),亚细胞也定位于细胞核。结论鼻咽癌组织ATF5蛋白表达水平显著高于鼻咽正常组织表达水平;局部复发鼻咽癌组织ATF5的表达水平显著高于初发鼻咽癌组织,提示鼻咽癌的复发可能源于ATF5蛋白的高表达;X线能促进鼻咽癌细胞ATF5蛋白表达显著上调,且亚细胞定位发生改变,提示ATF5可能参与鼻咽癌放疗抵抗。
Objective To observe the changes of activating transcription factor 5(ATF5) protein expression in tissues of local recurrent nasopharyngeal carcinoma,and further explore the correlation between ATF5 expression level and recurent nasopharyngeal carcinoma and its possible mechanisms.Methods The expression level of ATF5 protein in 6 cases of the same primary and recurrent nasopharyngeal carcinoma and normal nasopharyngeal tissues was compared by immunohistochemistry.Immunocytochemistry and cellular immunofluorescence were used to detect the effects of different doses of X-ray on the expression of ATF5 protein in nasopharyngeal carcinoma cell lines HONE-1.Results The expression level of ATF5 protein in nasopharyngeal carcinoma tissues was higher than that in normal nasopharyngeal tissues.The subcellular localization was mainly located in cytoplasm.The level of ATF5 protein expression in local recurrent nasopharyngeal carcinoma was higher than that in primary nasopharyngeal carcinoma.The subcellular localization was mainly located in the nucleus.X-ray could promote the up-regulation of ATF5 protein level in HONE-1 cells of nasopharyngeal carcinoma and the level of ATF5 protein expression was increased with the dose of X-ray irradiation.The subcellular localization was also located in the nucleus.Conclusion The level of ATF5 protein expression in nasopharyngeal carcinoma tissues is higher than that in nasopharyngeal normal tissues and the level of ATF5 expression in recurrent nasopharyngeal carcinoma tissues is higher than that in primary nasopharyngeal carcinoma tissues,which suggests that the recurrence of nasopharyngeal carcinoma might be ascribed to higher expression of ATF5.X-ray could promote the up-regulation of ATF5 expression in nasopharyngeal carcinoma HONE-1 cells,and the subcellular localization is also changed,which implies that ATF5 might be involved in radiotherapy resistance of nasopharyngeal carcinoma.
Objective To observe the changes of activating transcription factor 5(ATF5) protein expression in tissues of local recurrent nasopharyngeal carcinoma,and further explore the correlation between ATF5 expression level and recurent nasopharyngeal carcinoma and its possible mechanisms.Methods The expression level of ATF5 protein in 6 cases of the same primary and recurrent nasopharyngeal carcinoma and normal nasopharyngeal tissues was compared by immunohistochemistry.Immunocytochemistry and cellular immunofluorescence were used to detect the effects of different doses of X-ray on the expression of ATF5 protein in nasopharyngeal carcinoma cell lines HONE-1.Results The expression level of ATF5 protein in nasopharyngeal carcinoma tissues was higher than that in normal nasopharyngeal tissues.The subcellular localization was mainly located in cytoplasm.The level of ATF5 protein expression in local recurrent nasopharyngeal carcinoma was higher than that in primary nasopharyngeal carcinoma.The subcellular localization was mainly located in the nucleus.X-ray could promote the up-regulation of ATF5 protein level in HONE-1 cells of nasopharyngeal carcinoma and the level of ATF5 protein expression was increased with the dose of X-ray irradiation.The subcellular localization was also located in the nucleus.Conclusion The level of ATF5 protein expression in nasopharyngeal carcinoma tissues is higher than that in nasopharyngeal normal tissues and the level of ATF5 expression in recurrent nasopharyngeal carcinoma tissues is higher than that in primary nasopharyngeal carcinoma tissues,which suggests that the recurrence of nasopharyngeal carcinoma might be ascribed to higher expression of ATF5.X-ray could promote the up-regulation of ATF5 expression in nasopharyngeal carcinoma HONE-1 cells,and the subcellular localization is also changed,which implies that ATF5 might be involved in radiotherapy resistance of nasopharyngeal carcinoma.
引文
[1] 邹森.MEG3对鼻咽癌细胞转移能力的影响及相关机制的初步探究[J].遵义医学院学报,2018,41(3):336-343.
[2] 中国抗癌协会鼻咽癌专业委员会,李金高,陈晓钟,等.鼻咽癌复发、转移诊断专家共识[J].中华放射肿瘤学杂志,2018,27(1):7-15.
[3] Sears T K,Angelastro J M.The transcription factor ATF5:role in cellular differentiation,stress responses,and cancer[J].Oncotarget,2017,8(48):84595-84609.
[4] 冯光勇,张莹莹,张贵海.ATF5在鼻咽癌组织中的表达及临床意义[J].遵义医学院学报,2018,41(2):189-192.
[5] 韩非,卢泰祥.复发鼻咽癌的临床特点及挽救性治疗[J].中华耳鼻咽喉头颈外科杂志,2012,47 (3):261-264.
[6] Setton J,Han J,Kannarunimit D,et al.Long-term patterns of relapse and survival following definitive intensity-modulated radiotherapy for non-endemic nasopharyngeal carcinoma[J].Oral oncology,2016,53:67-73.
[7] Wang L,Guo Y,Xu J,et al.Clinical analysis of recurrence patterns in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy[J].The Annals of Otology,Rhinology,and Laryngology,2017,126(12):789-797.
[8] 李宁,杨卫兵.中晚期鼻咽癌放化疗综合治疗近期疗效观察[J].遵义医学院学报,2005,28(3):253-254.
[9] Gho J W,Ip W K,Chan K Y,et al.Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest[J].Cancer Research,2008,68(16):6743-6751.
[10] Ishihara S,Yasuda M,Ishizu A,et al.Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells[J].Oncotarget,2015,6(7):4602-4614.
[11]Nishioka T,Miyai Y,Haga H,et al.Novel function of transcription factor ATF5:blockade of p53-dependent apoptosis induced by ionizing irradiation[J].Cell Structure and Function,2009,34(1):17-22.
[12]Van Deursen J M.The role of senescent cells in ageing [J].Nature,2014,509(7501):439-446.
[13]Karpel-Massler G,Horst B A,Shu C,et al.A synthetic cell-penetrating dominant-negative ATF5 peptide exerts anticancer activity against a broad spectrum of treatment-resistant cancers[J].Clinical Cancer Research,2016,22(18):4698-4711.
[14]Nukuda A,Endoh H,Yasuda M,et al.Role of ATF5 in the invasive potential of diverse human cancer cell lines[J].Biochemical and Biophysical Research Communications,2016,474(3):509-514.
[2] 中国抗癌协会鼻咽癌专业委员会,李金高,陈晓钟,等.鼻咽癌复发、转移诊断专家共识[J].中华放射肿瘤学杂志,2018,27(1):7-15.
[3] Sears T K,Angelastro J M.The transcription factor ATF5:role in cellular differentiation,stress responses,and cancer[J].Oncotarget,2017,8(48):84595-84609.
[4] 冯光勇,张莹莹,张贵海.ATF5在鼻咽癌组织中的表达及临床意义[J].遵义医学院学报,2018,41(2):189-192.
[5] 韩非,卢泰祥.复发鼻咽癌的临床特点及挽救性治疗[J].中华耳鼻咽喉头颈外科杂志,2012,47 (3):261-264.
[6] Setton J,Han J,Kannarunimit D,et al.Long-term patterns of relapse and survival following definitive intensity-modulated radiotherapy for non-endemic nasopharyngeal carcinoma[J].Oral oncology,2016,53:67-73.
[7] Wang L,Guo Y,Xu J,et al.Clinical analysis of recurrence patterns in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy[J].The Annals of Otology,Rhinology,and Laryngology,2017,126(12):789-797.
[8] 李宁,杨卫兵.中晚期鼻咽癌放化疗综合治疗近期疗效观察[J].遵义医学院学报,2005,28(3):253-254.
[9] Gho J W,Ip W K,Chan K Y,et al.Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest[J].Cancer Research,2008,68(16):6743-6751.
[10] Ishihara S,Yasuda M,Ishizu A,et al.Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells[J].Oncotarget,2015,6(7):4602-4614.
[11]Nishioka T,Miyai Y,Haga H,et al.Novel function of transcription factor ATF5:blockade of p53-dependent apoptosis induced by ionizing irradiation[J].Cell Structure and Function,2009,34(1):17-22.
[12]Van Deursen J M.The role of senescent cells in ageing [J].Nature,2014,509(7501):439-446.
[13]Karpel-Massler G,Horst B A,Shu C,et al.A synthetic cell-penetrating dominant-negative ATF5 peptide exerts anticancer activity against a broad spectrum of treatment-resistant cancers[J].Clinical Cancer Research,2016,22(18):4698-4711.
[14]Nukuda A,Endoh H,Yasuda M,et al.Role of ATF5 in the invasive potential of diverse human cancer cell lines[J].Biochemical and Biophysical Research Communications,2016,474(3):509-514.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |