期刊文献+

子宫颈癌中Gli蛋白过表达的临床病理学意义 被引量:5

Clinicopathological significance of Gli proteins overexpression in uterine cervical cancers
暂未订购
导出
摘要 目的研究Gli蛋白检测在子宫颈癌及其癌前病变中的临床病理学意义,并分析Gli蛋白表达与HPV16型感染的关系。方法32例正常子宫颈上皮、71例子宫颈上皮内瘤变(CIN);其中CIN128例、CIN218例、CIN325例和80例子宫颈鳞状上皮癌(SCC)共183例存档蜡块选自延边大学医院、延边妇幼保健院和延边肿瘤医院病理科。应用PCR技术检测上述组织中HPV16型的感染,并用免疫组化方法在子宫颈病变组织芯片中检测Gli-1、Gli-2、Gli-3蛋白的表达情况。结果Gli-1和Gli-2蛋白呈胞质和胞核染色,Gli-3蛋白多数呈胞质染色。在子宫颈癌和癌前病变(CIN2/3)中,Gli-1~3呈强阳性,其阳性表达率均显著高于正常子宫颈黏膜上皮。80例子宫颈癌标本中HPV16阳性率是77.5%。在子宫颈癌组织中HPV16阳性组的Gli-1蛋白的胞质阳性率(85.5%,53/62)与强阳性率(85.5%,53/62)以及Gli-2蛋白的胞质阳性率(100%)与胞核强阳性率(100%)均高于HPV16阴性组(Gli-1胞质阳性率与强阳性率均为0,Gli-2胞质阳性率和胞核强阳性率分别为0和50%),差异具有统计学意义(P均<0.05);而3种蛋白表达率与患者的年龄、淋巴结转移、肿瘤学分期和临床分期均无关。结论Gli-1、Gli-2、Gli-3蛋白过表达可以作为子宫颈癌及其癌前病变的早期辅助诊断指标,Gli蛋白的表达水平与HPV16感染密切相关,且有望成为子宫颈癌靶向治疗的新靶点。 Purpose To investigate the significance of Gli proteins expression in uterine cervical lesions and its relationship with HPV 16 infection status. Methods Total 183 cases of cervical lesions, including 32 non-neoplastic cervix, 71 cervical intraepithelial neoplasia (28 CIN1, 18 CIN2,and 25 CIN3) and 80 squamons cell carcinomas (SCCs) were selected from the Department of Pathology, Yanbian University Hospital, Yanbian Women Hospital, and Yanbian Tumor Hospital. Gli-1 - 3 proteins expression was detected in tissue mieroarray by immunohistochemistry,and HPV 16 screening was performed by using PCR method. Results Gli-1 and Gli-2 were both cytoplasmic and nuclear staining pattern, but Gli-3 was mainly observed in the cytoplasm. The immunohistochemical staining showed that the expression rates of Gli-1, 2 and Gli-3 were significantly higher in cervical cancer and precursor lesions ( CIN2/3 ) than normal cervical epithelia. Meanwhile,HPV16 was positive in 77.5% of SCCs. In cervical cancer tissues, the expression rates of Gli-1 (both positive and strong positive rates of cytoplasmic pattern were 8.5.5% ) and Gli-2 (positive rate of cytoplasmic pattern was 100% ; strong positive rate of nuclear pattern was 100% ) were significantly higher in HPV16 positive group than in HPV16 negative group ( both positive and strong positive rates of Gli-1 cytoplasmic pattern were 0 ; positive rate of Gli2 cytoplasmic pattern was 0 ; strong positive rate of Gli-2 nuclear pattern was 50% ) ( P 〈 0. 05 ). Conclusions Gli-1 - 3 proteins of hedgehog signaling molecules might be a helpful marker for the early diagnosis and a potential therapeutic target for cervical cancers. Gli protein expression level is also related to the HPV16 infection status.
出处 《临床与实验病理学杂志》 CAS CSCD 北大核心 2009年第2期122-126,共5页 Chinese Journal of Clinical and Experimental Pathology
基金 国家教育部重点项目"新世纪优秀人才支持计划"(NCET-07-0734) 国家自然科学基金(30560047) 国家教育部留学回国人员科研启动基金(教外司留20071108) 吉林省科学发展计划杰出青年基金(20060103)
关键词 子宫肿瘤 Gli蛋白 乳头状瘤病毒 cervix neoplasms gli protein papillomavirus, human
  • 相关文献

参考文献15

  • 1Cohen M M.The hedgehog signaling network[J].Am J Med Genet,2003,123(1):5-28.
  • 2Jiang J.Regulation of Hh/Gli signaling by dual ubiquitin pathways[J].Cell Cycle,2006,5(21):2457-2463.
  • 3Greene F L,Page D L,Fleming I D,et al.American joint committee on Cancer staging manual[M].6th ed.New York:Springer,2002:293-298.
  • 4任香善,林贞花,吴群英,赵祎玮,玄延花,金仁仙.子宫颈癌△Np63蛋白表达的临床病理学意义[J].临床与实验病理学杂志,2006,22(6):646-648. 被引量:3
  • 5Lin Z H,Shen X H,Jin Z,et al.Human papillomavirus genotyping by oligonucleotide microarray and p16INK4A expression in the uterine cervical intraepithelial neoplasm and invasive carcinoma in Korean women[J].Pathol Int,2005,55:491-496.
  • 6Bai C B,Joyner A L.Gli1 can rescue the in vivo function of Gli2[J].Development,2001,128(24):5161-5172.
  • 7Persson M,Stamataki D,Te Welscher P,et al.Dorsal-ventral patterning of the spinal cord requires Gli3 trascriptional repressor activity[J].Genes Dev,2002,16(22):2865-2878.
  • 8Kenney A M,Rovitch D H.Sonic hedgehog prometes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precrusors[J].Mol Cell Biol,2000,20(23):9055-9067.
  • 9Regl G,Kasper M,Schnidar H,et al.Activation of the Bcl2 promoter in response to Hedgehog/Gli signal trasduction is predominantly mediated by Gli2[J].Cancer Res,2004,64(21):7724-7731.
  • 10Karhadkar S S,Bova G S,Abdallah N,et al.Hedgehog signalling in prostate regeneration,neoplasia and metastasis[J].Nature,2004,431(7009):707-712.

二级参考文献28

  • 1陈志荣,李兆申,屠振兴,高军,龚燕芳,金晶,满晓华.胰腺癌组织中PTCHmRNA的表达及其临床意义[J].世界华人消化杂志,2005,13(9):1147-1150. 被引量:2
  • 2陈志荣,李兆申,屠振兴,龚燕芳,金晶,满晓华.胰腺癌组织中SMO mRNA的表达及其临床意义[J].胰腺病学,2005,5(2):82-84. 被引量:4
  • 3邵建国,许国铭,屠振兴,高军,龚燕芳,许爱芳,满小华,吴红玉,金晶.胰腺癌组织中PTCH蛋白免疫组化检测[J].第二军医大学学报,2005,26(8):950-951. 被引量:6
  • 4桂建芳.RNA加工与细胞周期调控.北京:科学出版社,1998:103-30.
  • 5Sherr CJ.Cancer cell cycles.Science,1996,274:1672-7.
  • 6Graflund M, Sorbe B, Karlsson M. Immunohistochemical ex pressive of p53, bcl-2 and p21 (WAF1/CIP1) in early cervical carcinoma correlation with clinical outcome. Int J Gynecol Cancer,2002,12(3) : 290~8.
  • 7Murphy N, Ring M, Killalea AG, et al. p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep smears, J Clin Pathol, 2003,56(1): 56~63.
  • 8Sano T, Oyama T, Kashiwabara K, et al. Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions. Am J Pathol, 1998,153: 1741~8.
  • 9Riethdorf L, Riethdorf S, Lee KR, et al. Human papillomaviruses,expression of p16, and early endocervical glandular neoplasia. Hum Pathol, 2002,33(9) :899~904.
  • 10Wu G, Nomoto S, Hoque M O, et al. TAp63ct and △Np63α regulate transcription of genes with distinct biological functions in cancer and development [ J ]. Cancer Res, 2003,63:2351 - 2357.

共引文献29

同被引文献51

  • 1Eichberger T, Sander V, Schnidar H, et al. Overlapping and distinct transcriptional regulator properties of the Glil and Gli2 oncogenes [J ] . Genomics, 2006, 87 (5): 616.
  • 2Omenetti A, Diehl AM. The adventures of sonic hedgehog in development and repair. II. Sonic hedgehog and liver develop- ment, inflammation, and cancer [ J] . Am J Physiol Gastroi- ntest Liver Physiol, 2008, 294 (3) : 595.
  • 3Mazumdar T, De Vecchio J, Agyeman A, et al. The Gli genes as the molecular switch in disrupting hedgehog signaling in colon cancer [J] . Oncotarget, 2011, 2 (8) : 638.
  • 4Wang K, Pan L, Che X, et al. Glil inhibition induces cell - cycle arrest and enhanced apoptosis in brain glioma cell lines [J] . J Neurooneol, 2010, 98 (3) : 319.
  • 5Shahi MH, Rey JA, Castresana JS. The sonic hedgehog - Glil signaling pathway in brain tumor development [ J] . Expert Opin Ther Targets, 2012, 16 (12) : 1227.
  • 6Chen M, Carkner R, Buttyan R. The hedgehog/Gli signaling paradigm in prostate cancer [J 3 . Expert Rev Endocrinol Metab, 2011, 6 (3): 453.
  • 7Liao X, Siu MK, Au CW, et al. Aberrant activation of hedge- hog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation [ J] . Carcinogenesis, 2009, 30 (1): 131.
  • 8Chen X, Horiuchi A, Kikuchi N, et al. Hedgehog signal pathway is activated in ovarian carcinomas, correlating with cell proliferation: it's inhibition leads to growth suppression and apoptosis [J] . Cancer Sci, 2007, 98 (1): 68.
  • 9Bhattacharya R, Kwon J, Ali B, et al. Role of hedgehog sig- naling in ovarian cancer [J] . Clin Cancer Res, 2008, 14 (23) : 7659.
  • 10Xuan YH, Jung HS, Choi YL, et al. Enhanced expression of hedgehog signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions [J ] . Mod Pathol, 2006, 19 (8): 1139.

引证文献5

二级引证文献9

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