期刊文献+

卵巢透明细胞腺癌的DNA损伤应答反应 被引量:5

DNA Damage Response in Ovarian Clear Cell Adenocarcinoma
原文传递
导出
摘要 目的研究卵巢透明细胞腺癌的发生与DNA损伤应答之间的关系。方法对14例新鲜卵巢组织标本(正常卵巢组织3例,低分化卵巢肿瘤6例,透明细胞腺癌5例),采用X射线(2Gy)照射制备组织DNA损伤模型,分别对其进行组织冷冻切片,采用免疫荧光和Western免疫印迹方法检测DNA损伤应答反应。结果在X射线照射前,与正常卵巢组织细胞相比,透明细胞腺癌中存在大量内源性DNA损伤,X射线照射后组蛋白2A变体(H2AX)表现过度磷酸化,而损伤修复能力正常。p53结合蛋白1(53BP1)的激活与磷酸化的H2AX(γH2AX)不能共定位。结论卵巢透明细胞腺癌中DNA损伤异常激活,提示DNA损伤应答信号转导网络存在缺陷。 Objective To study the relationship between ovarian clear cell adenocarcinoma and DNA damage.Methods 14 samples were selected from clinical ovaian cases including 3 cases with normal ovarian tissue,6 cases with poorly differentiated ovarian tumor,5 cases with ovarian clear cell adenocarcinoma,treated by X-ray irradiation and frozen sections respectively.DNA damage response was analyzed by immunofluorescence and Western blot.Results Before X-ray irradiation,compared to normal ovarian tissue,a large number of endogenous damage existed in ovarian clear cell adenocarcinoma,and phosphorylation of histone family 2A variant(H2AX) was abnormally enhanced 1 hour after irradiation treatment,however,DNA repair was normal in ovarian clear cell adenocarcinoma.Phosphorylation of H2AX was dispensable for p53 binding protein l(53BP1) activation and couldn't be colocalized in clear-type ovarian cancer tissues.Conclusion The abnormal DNA damage activation implies that the network of DNA damage signaling pathway may be defective.
出处 《四川大学学报(医学版)》 CAS CSCD 北大核心 2012年第3期331-334,共4页 Journal of Sichuan University(Medical Sciences)
关键词 透明细胞腺癌 DNA损伤 磷酸化组蛋白2A变体 p53结合蛋白1 Ovarian clear cell adenocarcinoma DNA damage γH2AX 53BP1
  • 相关文献

参考文献14

  • 1Sugiyama T,Kamura T,Kigawa J,et al.Clinicalcharacteristics of clear cell carcinoma of the ovary:a distincthistologic type with poorprognosis and resistance to platinum-based chemotherapy.Cancer,2000;88(11):2584-2589.
  • 2Takano M,Kikuchi Y,Yaegashi N,et al.Clear cell carcinomaof the ovary:a retrospective multicentre experience of 254patients with complete sorgical staging.Br J Cancer,2006;94(10):1369-1374.
  • 3Chan JK,Teoh D,Hu JM,et al.Do clear cell ovariancarcinomas have poorer prognosis compared to other epithelialcell types A study of 1411clear cell ovarian cancers.GynecolOncol,2008;109(3):370-376.
  • 4Rouse J,Jackson SP.Interfaces between the detection,signaling,and repair of DNA damage.Science,2000;2297(5581):547-551.
  • 5Fernandez-Capetillo O,Celeste A,Nussenzweig A.Focusingon foci:H2AX and the recruitment of DNA-damage responsefactors.Cell Cycle,2003;2(5):426-427.
  • 6Paull TT,Rogakou EP,Yamazaki V,et al.A critical role forhistone H2AX in recruitment of repair factors to nuclear fociafter DNA damage.Curr Biol,2000;10(15):886-895.
  • 7Celeste A,Fernandez-Capetillo O,Kruhlak MJ,et al.HistoneH2AX phosphorylation is dispensable for the initial recognitionof DNA breaks.Nat Cell Biol,2003;5(7):675-679.
  • 8Swenberg JA,Lu K,Benjamin C,et al.Endogenous versusexogenous DNA adducts:their role in carcinogenesis,epidemiology,and risk assessment.Toxicol Sci,2011;120(Suppl 1):S130-145.
  • 9Laiho M,Latonen L.Cell cycle control,DNA damagecheckpoints and cancer.Ann Med,2003;35(6):391-397.
  • 10Bartek J,Bartkova J,Lukas J.DNA damage signalling guardsagainst activated oncogenes and tumour progression.Oncogene,2007;26(56):7773-7779.

同被引文献81

  • 1Fasching PA, Gayther S, Pearce L, et al. Role of genetic pol- ymorphisms and ovarian cancer susceptibility [J] . Mol On- col, 2009, 3 (2): 171-181.
  • 2Swenberg JA, Lu K, Benjamin C, et al. Endogenous versus exogenous DNA adducts: their role in carcinogenesis epidemi- ology, and risk assessment [J] . Toxicol Sci, 2011, 120 ( Suppl 1 ) : S130 - S145.
  • 3Metivier R, Gallais R, Tiffoche C, et al. Cyclical DNA meth- ylation of a transcriptionally active promoter [ J ] . Nature, 2008, 452 (7183): 45-50.
  • 4Asadollahi R, Hyde AC, Zhong XY. Epigenetics of ovarian cancer: from the lab to the clinic [J] . Gynecol Oncol, 2010, 118 (1): 81-87.
  • 5Mchaelson R, Keshet I, Straussman R, et al. Genome - wide denovo methylation in epithelial ovarian cancer [J] . Int J Gy- necol Cancer, 2011, 21 (2): 269-279.
  • 6Watts GS, Futscher BW, Holtan N, et al. DNA methylation changes in ovarian cancer are cumulative with disease progres- sion and identify tumor stage [J] . BMC Med Genomics, 2008, 1 (1): 47.
  • 7Chaudhry P, Srinivasan R, Patel FD. Utility of gene promoter methylation in prediction of response to platinum - based chem- otherapy in epithelial ovarian cancer [ J ] . Cancer Invest, 2009, 27 (8): 877-884.
  • 8Ma L, Guo Q, Ma Y, et al. Clinicopathological implications of inactivation of RASSF1A in serous epithelial ovarian cancer [J] . Eur J Gynaecol Oncol, 2009, 30 (4) : 370 -374.
  • 9Hesson LB, Cooper WN, Latif F. The role of RASSF1A methylation in cancer [J] . Dis Markers, 2007, 23 (1/ 2) : 73 -87.
  • 10Kimura S, Naganuma S, Susuki D, et al. Expression of mi- croRNAs in squamous cell carcinoma of human head and neck and the esophagus: miR- 205 and miR- 21 are specific markers for HNSCC and ESCC [J] . Oneol Rep, 2010, 23 (6) : 1625 - 1633.

引证文献5

二级引证文献6

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部