Proto-oncogene Wip1, a member of a new family of proliferative genes in NSCLC and its clinical significance

被引:9
作者
Fu, Zhanzhao [1 ]
Sun, Guogui [1 ,2 ]
Gu, Tao [1 ]
机构
[1] First Hosp Qinhuangdao, Dept Tumor, Qinhuangdao 066000, Hebei Province, Peoples R China
[2] Tangshan Peoples Hosp, Dept Chemoradiotherapy, Tangshan 063000, Peoples R China
关键词
Wip1; NSCLC carcinoma; Immunohistochemistry; Reverse transcription-polymerase chain reaction; Western blot; NF-KAPPA-B; EXPRESSION; PPM1D;
D O I
10.1007/s13277-013-1382-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study aimed to analyze the expression, clinical significance of proto-oncogene in non small cell lung cancer (NSCLC), and the biological effect in its cell line by siRNA targeting wild-type p53-induced phosphatase 1 (Wip1). Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were, respectively, used to analyze Wip1 protein expression in 75 cases of NSCLC and normal tissues to study the relationship between Wip1 expression and clinical parameters. Wip1 siRNA was transiently transfected into papillary NSCLC H1299 cell by liposome-mediated method and was detected by RT-PCR and Western blot. MTT assay, cell apoptosis, and cell cycle were also conducted as to the influence of the downregulated expression of Wip1 that might be found on H1299 cells biological effect. The positive rates of Wip1 protein was 69.3 % in NSCLC tissues but 16.0 % expressed in normal tissues (P < 0.05). The relative content of Wip1 mRNA was 0.785 +/- 0.062 and 0.147 +/- 0.020 in NSCLC tissues and normal tissues, respectively, with significant differences between the two types (P < 0.05). There were no significant differences between Wip1 expression and sex, age, tumor size, and pathological types (P > 0.05). However, there were significant differences between Wip1 expression and lymph node metastasis, clinical stages, and tumor differentiation (P < 0.05). Individuals with positive and negative levels of Wip1 expression showed were statistically significant differences in the 5-year overall survival rate (P < 0.05). RT-PCR and Western blot showed that H1299 cell transfected Wip1 siRNA had a lower relative expressive content than normal cell (P < 0.05). MTT assay, cell apoptosis, and cell cycles demonstrated that H1299 cell transfected Wip1 siRNA had a lower survival fraction, higher cell apoptosis, more percentage of the G0/G1 phases, and lower cells in the S phases (P < 0.05). Wip1 protein and mRNA were increased in NSCLC, specifically in lymph node metastasis, clinical stages, and tumor differentiation. Wip1 may be involved in the biological processes of NSCLC cell proliferation, cell apoptosis, and cell cycle.
引用
收藏
页码:2975 / 2981
页数:7
相关论文
共 19 条
  • [1] [Anonymous], CHIN J EXP SURG
  • [2] [Anonymous], CHIN J NEUROL ONCOL
  • [3] Maternal Wnt/β-Catenin Signaling Coactivates Transcription through NF-κB Binding Sites during Xenopus Axis Formation
    Armstrong, Neil J.
    Fagotto, Francois
    Prothmann, Christian
    Rupp, Ralph A. W.
    [J]. PLOS ONE, 2012, 7 (05):
  • [4] p53 regulates LIF expression in human medulloblastoma cells
    Baxter, Euan W.
    Milner, Jo
    [J]. JOURNAL OF NEURO-ONCOLOGY, 2010, 97 (03) : 373 - 382
  • [5] Increased wild-type p53-induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma
    Fuku, Takeichi
    Semba, Shuho
    Yutori, Hirokazu
    Yokozaki, Hiroshi
    [J]. PATHOLOGY INTERNATIONAL, 2007, 57 (09) : 566 - 571
  • [6] Non-small-cell lung cancer
    Goldstraw, Peter
    Ball, David
    Jett, James R.
    Le Chevalier, Thierry
    Lim, Eric
    Nicholson, Andrew G.
    Shepherd, Frances A.
    [J]. LANCET, 2011, 378 (9804) : 1727 - 1740
  • [7] Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23
    Li, J
    Yang, Y
    Peng, Y
    Austin, RJ
    van Eyndhoven, G
    Nguyen, KCQ
    Gabriele, T
    McCurrach, ME
    Marks, JR
    Hoey, T
    Lowe, SW
    Powers, S
    [J]. NATURE GENETICS, 2002, 31 (02) : 133 - 134
  • [8] [梁朝辉 LIANG Chaohui], 2011, [基础医学与临床, Basic & Clinical Medicine], V31, P430
  • [9] Nuclear Factor-κB (NF-κB) Is a Novel Positive Transcriptional Regulator of the Oncogenic Wip1 Phosphatase
    Lowe, Julie M.
    Cha, Hyukjin
    Yang, Qian
    Fornace, Albert J., Jr.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (08) : 5249 - 5257
  • [10] Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma
    Mendrzyk, F
    Radlwimmer, B
    Joos, S
    Kokocinski, F
    Benner, A
    Stange, DE
    Neben, K
    Fiegler, H
    Carter, NP
    Reifenberger, G
    Korshunov, A
    Lichter, P
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (34) : 8853 - 8862