Reversing effect of exogenous WWOX gene expression on malignant phenotype of primary cultured lung carcinoma cells

被引:6
作者
Zhou Yu-long [1 ]
Li Yue-chuan [1 ]
Shou Feng [1 ]
Liu Chang-qi [1 ]
Pu Yong [2 ]
Tang Hua [2 ]
机构
[1] Tianjin Chest Hosp, Dept Chest Internal Med, Tianjin 300051, Peoples R China
[2] Tianjin Med Univ, Tianjin Cent Lab Life Sci, Tianjin 300070, Peoples R China
关键词
WWOX gene; primary cultured lung carcinoma cells; transfection; TUMOR-SUPPRESSOR; PROTEIN EXPRESSION; CANCER; FRA16D; PROGRESSION;
D O I
10.3760/cma.j.issn.0366-6999.2010.05.020
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Whether WW domain containing oxidoreductase (WWOX) gene is a tumor-suppressor is still controversial. Some researchers found that the transcription of the WWOX gene was lacking not only in tumor tissues but also in non-tumorous tissues and sometimes in normal tissues. Hence it is important to explore the role of the expression of the exogenous WWOX gene in the proliferation and apoptosis of primary cultured lung carcinoma cells. Methods Lipofection technique was used to determine primary cultured lung carcinoma cells containing the highly expressed exogenous WWOX gene and primary cultured cells with vectors as controls. An animal model of lung cancer was made by subcutaneous implantation of tumor cells into nude mice. RT-PCR, Western blotting, flow cytometry, and TUNEL were used to detect the transcription, expression of the exogenous gene and the effect of the expression of targeted genes on the proliferation and apoptosis of the primary cultured lung carcinoma cells. Results The growth, clone formation rate (CFR) ((5.33 +/- 1.53)%) of the primary lung cancer cells transfected with the WWOX gene, tumor size and weight were significantly lower than those of the non-transfected lung cancer cells (CFR: (14.33 +/- 1.53)%) and the primary lung cancer cells transfected with blank plasmids (CFR: (11.00 +/- 1.73)%, P<0.05). The apoptosis level of primary lung cancer cells transfected with the WWOX gene ((40.72 +/- 5.20)%) was significantly higher than that of the non-transfected lung cancer cells ((2.76 +/- 0.02)%) and the primary lung cancer cells transfected with blank plasmids ((2.72 +/- 0.15)%, P<0.05). Conclusion The expression of the exogenous WWOX gene can significantly inhibit the proliferation of lung cancer cells and induce their apoptosis, suggesting that the WWOX gene possesses tumor-suppressing effect. Chin Med J 2010;123(5):615-620
引用
收藏
页码:615 / 620
页数:6
相关论文
共 21 条
  • [1] Inactivation of the WWOX gene accelerates forestomach tumor progression in vivo
    Aqeilan, Rami I.
    Hagan, John P.
    Aqeilan, Haifa A.
    Pichiorri, Flavia
    Fong, Louise Y. Y.
    Croce, Carlo M.
    [J]. CANCER RESEARCH, 2007, 67 (12) : 5606 - 5610
  • [2] Functional association between Wwox tumor suppressor protein and p73, a p53 homolog
    Aqeilan, RI
    Pekarsky, Y
    Herrero, JJ
    Palamarchuk, A
    Letofsky, J
    Druck, T
    Trapasso, F
    Han, SY
    Melino, G
    Huebner, K
    Croce, CM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (13) : 4401 - 4406
  • [3] Loss of WWOX expression in gastric carcinoma
    Aqeilan, RI
    Kuroki, T
    Pekarsky, Y
    Albagha, O
    Trapasso, F
    Baffa, R
    Huebner, K
    Edmonds, P
    Croce, CM
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (09) : 3053 - 3058
  • [4] Bednarek AK, 2000, CANCER RES, V60, P2140
  • [5] Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity
    Cantor, Joshua P.
    Iliopoulos, Dimitrios
    Rao, Atul S.
    Druck, Teresa
    Semba, Shuho
    Han, Shuang-Yin
    McCorkell, Kelly A.
    Lakshman, Thiru V.
    Collins, Joshua E.
    Wachsberger, Phyllis
    Friedberg, Joseph S.
    Huebner, Kay
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (01) : 24 - 31
  • [6] Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity
    Chang, NS
    Pratt, N
    Heath, J
    Schultz, L
    Sleve, D
    Carey, GB
    Zevotek, N
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (05) : 3361 - 3370
  • [7] Gourley C, 2005, INT J ONCOL, V26, P1681
  • [8] The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma -: Correlations with clinical features
    Guler, G
    Uner, A
    Guler, N
    Han, SY
    Iliopoulos, D
    Hauck, WW
    McCue, P
    Huebner, K
    [J]. CANCER, 2004, 100 (08) : 1605 - 1614
  • [9] Mangelsdorf M, 2000, CANCER RES, V60, P1683
  • [10] Role of the WWOX gene, encompassing fragile region FRA16D, in suppression of pancreatic carcinoma cells
    Nakayama, Shunji
    Semba, Shuho
    Maeda, Naoko
    Aqeilan, Rami I.
    Huebner, Kay
    Yokozaki, Hiroshi
    [J]. CANCER SCIENCE, 2008, 99 (07) : 1370 - 1376