原癌基因Pokemon及核转录因子E2F3在喉鳞癌中的表达及其临床意义

The Expression of Pokemon and E2F3 in Laryngeal Squamous Cell Carcinoma and Their Clinical Significance

刘丽英;王琳;闫完平;周合心;

1:临汾职业技术学院附属医院耳鼻咽喉科

2:临汾市人民医院耳鼻咽喉科

3:临汾市第四人民医院耳鼻咽喉科

4:临汾市第二人民医院五官科

摘要
目的探讨POK红系髓性致癌因子(POK erythroid myeloid ontogenic factor,Pokemon)及核转录因子E2F3(E2Ftranscrip tion factor 3)在喉鳞癌中的表达及其临床意义。方法采用免疫组化Max Vision二步法观察61例喉鳞癌组织及46例癌旁正常喉黏膜组织中Pokemon及E2F3的表达,并结合患者年龄、性别、原发部位、TNM分期、临床分期及预后之间的关系进行分析。结果 Pokemon及E2F3在喉鳞癌组织中的阳性表达率明显高于癌旁正常喉黏膜组织中的阳性表达率(P<0.001);颈淋巴结转移(N+)、中低分化、临床晚期(Ⅲ+Ⅳ)喉鳞癌患者中Pokemon及E2F3表达强度增强(P<0.05);Pokemon及E2F3阳性表达患者的5年累积生存率较阴性表达患者低(P<0.05)。结论 Pokemon与E2F3在喉鳞癌组织中高表达,并与其预后不良相关。两者可能在喉鳞癌发生及恶性进展过程中发挥重要作用,有望成为喉鳞癌发病机制及分子靶向治疗的新指标。
关键词
喉鳞状细胞癌;POK红系髓性致癌因子;核转录因子E2F3;预后
基金项目(Foundation):
作者
刘丽英;王琳;闫完平;周合心;
参考文献

1季文樾,杜强,关超,等.1115例喉癌患者的生存分析[J].中华耳鼻咽喉科杂志,2004,39:17.

2 Maeda T,Hobbs RM,Merghoub T,et al.Role of the proto-oncogene Pokemon in cellular transformation and ARF re-pression[J].Nature,2005,433:278.

3 Leone G,DeGregori J,Yan Z,et al.E2F3activity is regula-ted during the cell cycle and is required for the induction of S phase[J].Genes Dev,1998,12:2 120.

4 Zindy F,Williams RT,Baudino TA,et al.Arf tumor sup-pressor promoter monitors latent oncogenic signals in vivo[J].Proc Natl Acad Sci U S A,2003,100:15 930.

5 Birner P,Schindl M,Obermair A,et al.Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer[J].Cancer Res,2000,60:4 693.

6 Morrison DJ,Pendergrast PS,Stavropoulos P,et al.FBI-1,a factor that binds to the HIV-1inducer of short transcripts(IST),is a POZ domain protein[J].Nucleic Acids Res,1999,27:1 251.

7 Lee DK,Suh D,Edenberg HJ,et al.POZ domain transcrip-tion factor,FBI-1,represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA bind-ing activity of Sp1[J].J Biol Chem,2002,277:26 761.

8 Koken MH,Reid A,Quignon F,et al.Leukemia-associated retinoic acid receptor alpha fusion partners,PML and PLZF,heterodimerize and colocalize to nuclear bodies[J].Proc Natl Acad Sci U S A,1997,94:10 255.

9 Chen WY,Zeng X,Carter MG,et al.Heterozygous disrup-tion of Hic1predisposes mice to a gender-dependent spectrumof malignant tumors[J].Nat Genet,2003,33:197.

10 Kong LJ,Chang JT,Bild AH,et al.Compensation and spe-cificity of function within the E2Ffamily[J].Oncogene,2007,26:321.

11 Kort EJ,Farber L,Tretiakova M,et al.The E2F3-On-comir-1axis is activated in Wilms'tumor[J].Cancer Res,2008,68:4 034.

12 Cunningham JM,Vierkant RA,Sellers TA,et al.Cell cycle genes and ovarian cancer susceptibility:a tagSNP analysis[J].Br J Cancer,2009,101:1 461.

13胡力仁,吴长利,胡海龙,等.E2F3和AR在前列腺癌组织中的表达及意义[J].天津医药,2012,40:1.

14 Clark PA,Llanos S,Peters G.Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2[J].On-cogene,2002,21:4 498.

15赵凌冰,古丽那尔.阿布拉江,李晓梅,等.在口腔鳞状细胞癌中Pokemon、Ku70的表达及临床病理学意义的研究[J].口腔医学研究,2011,27:994.

16 Zhao ZH,Wang SF,Yu L,et al.Expression of transcription factor Pokemon in non-small cell lung cancer and its clinical significance[J].Chin Med J(Engl),2008,121:445.

17高伟,隋军,李晓江,等.Pokemon在鼻咽癌中的表达及临床意义[J].现代肿瘤医学,2009,17:37.

18 Ziebold U,Lee EY,Bronson RT,et al.E2F3loss has oppo-sing effects on different pRB-deficient tumors,resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas[J].Mol Cell Biol,2003,23:6 542.

19 Schumacher U,Adam E,Feldhaus S,et al.Cell differentia-tion and chemotherapy influence p53and Mdm2immunoreac-tivity in human HT29colon cancer cells grown in scid mice[J].Cancer Lett,2001,166:215.

20 Ginsberg D.E2F3-a novel repressor of the ARF/p53path-way[J].Dev Cell,2004,6:742.

21赵智宏,王胜发,丛德刚,等.非小细胞肺癌中pokemon表达与p 14ARF、bcl-2的相关性及对预后的影响[J].肿瘤,2008,28:121.