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Article

MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis

  • Authors:
    • Wenxiang Bi
    • Yuping Wei
    • Jinxiang Wu
    • Gaoying Sun
    • Yuanfang Guo
    • Qiang Zhang
    • Liang Dong
  • View Affiliations / Copyright

    Affiliations: Institute of Biochemistry and Molecular Biology, School of Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
  • Pages: 1533-1539
    |
    Published online on: January 29, 2013
       https://doi.org/10.3892/or.2013.2258
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Abstract

MAPK-activating death domain protein (MADD) binds to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor and acts as a key downstream mediator in the TRAIL-induced apoptosis pathway. The aim of this study was to evaluate the expression of MADD in normal human and adenocarcinoma tissues of the lungs and its influence on proliferation and apoptosis of A549 human lung adenocarcinoma cells. Immunohistochemistry was carried out to detect the expression of MADD in normal and tumor tissues of the lungs. Expression of the MADD gene in A549 cells was measured by reverse transcription-polymerase chain reaction. A549 cells were transfected with plasmids carrying the DNA fragment encoding MADD and lentiviral vectors used for RNA interference, respectively. MADD expression in the transfected A549 cells was determined by western blotting. Proliferation and apoptosis were detected using MTT assay and flow cytometry, respectively. It was found that non-small cell lung cancer tissues expressed MADD at higher levels compared to normal lung tissues, and the level of MADD in lung adenocarcinoma was higher compared to that in lung squamous cell carcinoma. MADD was expressed in A549 cells. Both introduction of the DNA fragment encoding MADD and RNA interference targeting MADD effectively altered levels of MADD in the A549 cells. Overexpression of MADD in the A549 cells inhibited apoptosis and increased survival whereas abrogation of MADD promoted apoptosis and reduced cell proliferation. These results suggest that MADD may be a potential therapeutic target for lung adenocarcinoma therapy involving the TRAIL-induced apoptosis pathway.
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1 

Niemoeller OM and Belka C: Radiotherapy and TRAIL for cancer therapy. Cancer Lett. July 12–2011.(Epub ahead of print).

2 

Johstone RW, Frew AJ and Smyth MJ: The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 10:782–798. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Kruyt FA: TRAIL and cancer therapy. Cancer Lett. 263:14–25. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Al-Zoubi AM, Efimova EV, Kaithamana S, Martinez O, El-Idrissi Mel-ADogan RE and Prabhakar BS: Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3. J Biol Chem. 276:47202–47211. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Li P, Jayarama S, Ganesh L, et al: Akt-phosphorylated mitogen-activated kinase-activating death domain protein (MADD) inhibits TRAIL-induced apoptosis by blocking Fas-associated death domain (FADD) association with death receptor 4. J Biol Chem. 285:22713–22722. 2010. View Article : Google Scholar

6 

Chow VT, Lim KM and Lim D: The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p11.21–p11.22. Genome. 41:543–552. 1998.PubMed/NCBI

7 

Efimova EV, Al-Zoubi AM, Martinez O, et al: IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs. Oncogene. 23:1076–1087. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Mulherkar N, Prasad KV and Prabhakar BS: MADD/DENN splice variant of the IG20 gene is a negative regulator of caspase-8 activation. Knockdown enhances TRAIL-induced apoptosis of cancer cells. J Biol Chem. 282:11715–11721. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Mulherkar N, Ramaswamy M, Mordi DC and Prabhakar BS: MADD/DENN splice variant of the IG20 gene is necessary and sufficient for cancer cell survival. Oncogene. 25:6252–6261. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Schievella AR, Chen JH, Graham JR and Lin LL: MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase. J Biol Chem. 272:12069–12075. 1997. View Article : Google Scholar

11 

Lee MT, Coburn GA, McClure MO and Cullen BR: Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus vector. J Virol. 77:11964–11972. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Demirhan O, Tastemir D, Hastürk S, Kuleci S and Hanta I: Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: fluorescence in situ hybridization and cytogenetic studies. Cancer Epidemiol. 34:472–477. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Lee YL, Kuo WH, Lin CW, et al: Association of genetic polymorphisms of CXCL12/SDF1 gene and its receptor, CXCR4, to the susceptibility and prognosis of non-small cell lung cancer. Lung Cancer. 73:147–152. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Rosell R, Moran T, Queralt C, et al: Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 361:958–967. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Pukac L, Kanakaraj P, Humphreys R, et al: HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumor types in vitro and in vivo. Br J Cancer. 92:1430–1441. 2005. View Article : Google Scholar : PubMed/NCBI

16 

LeBlanc HN and Ashkenazi A: Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ. 10:66–75. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Riccioni R, Pasquini L, Mariani G, et al: TRAIL decoy receptors mediate resistance of acute myeloid leukemia cells to TRAIL. Haematologica. 90:612–624. 2005.PubMed/NCBI

18 

Morizot A, Mérino D, Lalaoui N, et al: Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level. Cell Death Differ. 18:700–711. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Zhang L and Fang B: Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther. 12:228–237. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Hopkins-Donaldson S, Ziegler A, Kurtz S, et al: Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ. 10:356–364. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Ray S, Bucur O and Almasan A: Sensitization of prostate carcinoma cells to Apo2L/TRAIL by a Bcl-2 family protein inhibitor. Apoptosis. 10:1411–1418. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Trauzold A, Siegmund D, Schniewind B, et al: TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene. 25:7434–7439. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Cunningham SJ: Cloning and characterization of a novel cDNA isolated from human β cells. Doctoral dissertation. The University of Texas, Medical Branch; 1996

24 

Chow VT and Lee SS: DENN, a novel human gene differentially expressed in normal and neoplastic cells. DNA Seq. 6:263–273. 1996.PubMed/NCBI

25 

Li LC, Sheng JR, Mulherkar N, Prabhakar BS and Meriggioli MN: Regulation of apoptosis and caspase-8 expression in neuroblastoma cells by isoforms of the IG20 gene. Cancer Res. 68:7352–7361. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Miyoshi J and Takai Y: Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection. Trends Mol Med. 10:476–480. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Niwa S, Tanaka Y and Hirokawa N: KIF1Bbeta- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through DENN/MADD. Nat Cell Biol. 10:1269–1279. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Yamaguchi K, Tanaka M, Mizoguchi A, et al: A GDP/GTP exchange protein for the Rab3 small G protein family up-regulates a postdocking step of synaptic exocytosis in central synapses. Proc Natl Acad Sci USA. 99:14536–14541. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Del Villar K and Miller CA: Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer’s disease brain and hippocampal neurons. Proc Natl Acad Sci USA. 101:4210–4215. 2004.PubMed/NCBI

30 

Kurada BR, Li LC, Mulherkar N, Subramanian M, Prasad KV and Prabhakar BS: MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment. J Biol Chem. 284:13533–13541. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Allaire PD, Marat AL, Dall’Armi C, Di Paolo G, McPherson PS and Ritter B: The connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes. Mol Cell. 37:370–382. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Prabhakar BS, Mulherkar N and Prasad KV: Role of IG20 splice variants in TRAIL resistance. Clin Cancer Res. 14:347–351. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Coppola T, Perret-Menoud V, Gattesco S, et al: The death domain of Rab3 guanine nucleotide exchange protein in GDP/GTP exchange activity in living cells. Biochem J. 362:273–279. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Lim KM, Yeo WS and Chow VT: Antisense abrogation of DENN expression induces apoptosis of leukemia cells in vitro, causes tumor regression in vivo and alters the transcription of genes involved in apoptosis and the cell cycle. Int J Cancer. 109:24–37. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Efimova E, Martinez O, Lokshin A, Arima T and Prabhakar BS: IG20, a MADD splice variant, increases cell susceptibility to gamma-irradiation and induces soluble mediators that suppress tumor cell growth. Cancer Res. 63:8768–8776. 2003.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Bi W, Wei Y, Wu J, Sun G, Guo Y, Zhang Q and Dong L: MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis. Oncol Rep 29: 1533-1539, 2013.
APA
Bi, W., Wei, Y., Wu, J., Sun, G., Guo, Y., Zhang, Q., & Dong, L. (2013). MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis. Oncology Reports, 29, 1533-1539. https://doi.org/10.3892/or.2013.2258
MLA
Bi, W., Wei, Y., Wu, J., Sun, G., Guo, Y., Zhang, Q., Dong, L."MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis". Oncology Reports 29.4 (2013): 1533-1539.
Chicago
Bi, W., Wei, Y., Wu, J., Sun, G., Guo, Y., Zhang, Q., Dong, L."MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis". Oncology Reports 29, no. 4 (2013): 1533-1539. https://doi.org/10.3892/or.2013.2258
Copy and paste a formatted citation
x
Spandidos Publications style
Bi W, Wei Y, Wu J, Sun G, Guo Y, Zhang Q and Dong L: MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis. Oncol Rep 29: 1533-1539, 2013.
APA
Bi, W., Wei, Y., Wu, J., Sun, G., Guo, Y., Zhang, Q., & Dong, L. (2013). MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis. Oncology Reports, 29, 1533-1539. https://doi.org/10.3892/or.2013.2258
MLA
Bi, W., Wei, Y., Wu, J., Sun, G., Guo, Y., Zhang, Q., Dong, L."MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis". Oncology Reports 29.4 (2013): 1533-1539.
Chicago
Bi, W., Wei, Y., Wu, J., Sun, G., Guo, Y., Zhang, Q., Dong, L."MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis". Oncology Reports 29, no. 4 (2013): 1533-1539. https://doi.org/10.3892/or.2013.2258
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