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Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy

  1. Author:
    Su, D. M.
    Zhang, Q. Y.
    Wang, X. X.
    He, P.
    Zhu, Y.
    Zhao, J. X.
    Rennert, O. M.
    Su, Y. A.
  2. Author Address

    Su, David M.; Zhang, Qiuyang, Wang, Xuexi, Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Su, David M.; Zhang, Qiuyang, Wang, Xuexi, Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. [Wang, Xuexi, Zhao, Jianxiong] Lanzhou Univ, Sch Med Sci, Inst Chinese Western Integrat Med, Lanzhou 730000, Gansu, Peoples R China. [He, Ping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hemostasis, Bethesda, MD 20892 USA. [Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Gen, NIH, Bethesda, MD USA. [Zhu, Yuelin Jack] NCI Frederick, Sci Applicat Int Corp Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA.
    1. Year: 2009
  1. Journal: Molecular Cancer Therapeutics
    1. 8
    2. 5
    3. Pages: 1292-1304
  2. Type of Article: Article
  1. Abstract:

    Human malignant melanoma has poor prognosis because of resistance to apoptosis and therapy. We describe identification of the expression profile of 1,037 mitochondria-focused genes and 84 survival-apoptosis genes in 21 malignant melanoma cell lines and 3 normal melanocyte controls using recently developed hMitChip3 cDNA micro-arrays. Unsupervised hierarchical clustering analysis of 1,037 informative genes, and 84 survival-apoptosis genes, classified these malignant melanoma cell lines into type A (n = 12) and type B (n = 9). Three hundred fifty-five of 1,037 (34.2%) genes displayed significant (P:5 0.030, false discovery rate <= 3.68%) differences ( +/->= 2.0-fold) in average expression, with 197 genes higher and 158 genes lower in type A than in type B. Of 84 genes with known survival-apoptosis functions, 38 (45.2%) displayed the significant (P < 0.001, false discovery rate < 0.15%) difference. Antiapoptotic (BCL2, BCL2A1, PPARD, and RAF1), antioxidant (MT3, PRDX5, PRDX3, GPX4, GLRX2, and GSR), and proapoptotic (BAD, BNIP1, APAF1, BNIP3L, CASP7, CYCS, CASP1, and VDAC1) genes expressed at higher levels in type A than in type B, whereas the different set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1), antioxidant [HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1, CASP2, CASP4, PDCD5, HTRA2 SEPT4, TNFSF10, and PRODH) genes expressed at lower levels in type A than in type B. Microarray data were validated by quantitative reverse transcription-PCR. These results showed the presence of two types of malignant melanoma, each with a specific set of dysregulated survival-apoptosis genes, which may prove useful for development of new molecular targets for therapeutic intervention and novel diagnostic biomarkers for treatment and prognosis of malignant melanoma. [Mol Cancer Ther 2009,8(5):1292-1304]

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  1. DOI: 10.1158/1535-7163.mct-08-1030
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