E2F1 in Melanoma Progression and Metastasis

被引:107
作者
Alla, Vijay [1 ]
Engelmann, David [1 ]
Niemetz, Annett [1 ]
Pahnke, Jens [2 ]
Schmidt, Anke [1 ]
Kunz, Manfred [3 ]
Emmrich, Stephan [1 ]
Steder, Marc [1 ]
Koczan, Dirk [4 ]
Puetzer, Brigitte M. [1 ]
机构
[1] Univ Rostock, Dept Vectorol & Expt Gene Therapy, Biomed Res Ctr, D-18057 Rostock, Germany
[2] Univ Rostock, Dept Neurol, D-18057 Rostock, Germany
[3] Univ Rostock, Dept Dermatol & Venereol, D-18057 Rostock, Germany
[4] Univ Rostock, Mol Immunol Unit, Inst Immunol, D-18057 Rostock, Germany
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2010年 / 102卷 / 02期
关键词
GROWTH-FACTOR RECEPTOR; TRANSCRIPTION FACTOR E2F-1; CELL LUNG-CARCINOMA; HUMAN COLON-CANCER; MALIGNANT-MELANOMA; TUMOR PROGRESSION; GENE-EXPRESSION; CYCLIN D1; OVEREXPRESSION; PROLIFERATION;
D O I
10.1093/jnci/djp458
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Metastases are responsible for cancer deaths, but the molecular alterations leading to tumor progression are unclear. Overexpression of the E2F1 transcription factor is common in high-grade tumors that are associated with poor patient survival. To investigate the association of enhanced E2F1 activity with aggressive phenotype, we performed a gene-specific silencing approach in a metastatic melanoma model. Knockdown of endogenous E2F1 via E2F1 small hairpin RNA [shRNA) expression increased E-cadherin expression of metastatic SK-Mel-147 melanoma cells and reduced their invasive potential but not their proliferative activity. Although growth rates of SK-Mel-147 and SK-Mel-103 xenograft tumors expressing E2F1 shRNA or control shRNA were similar, mice implanted with cells expressing E2F1 shRNA had a smaller area of metastases per lung than control mice (n=3 mice per group; 5% vs 46%, difference=41%, 95% confidence interval=15% to 67%; P = .01; one-way analysis of variance). We identified epidermal growth factor receptor as a direct target of E2F1 and demonstrated that inhibition of receptor signaling abrogates E2F1-induced invasiveness, emphasizing the importance of the E2F1-epidermal growth factor receptor interaction as a driving force in melanoma progression that may serve as a paradigm for E2F1-induced metastasis in other human cancers.
引用
收藏
页码:127 / 133
页数:7
相关论文
共 53 条
  • [1] Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions
    Barr, Sharon
    Thomson, Stuart
    Buck, Elizabeth
    Russo, Suzanne
    Petti, Filippo
    Sujka-Kwok, Izabela
    Eyzaguirre, Alexandra
    Rosenfeld-Franklin, Maryland
    Gibson, Neil W.
    Miglarese, Mark
    Epstein, David
    Iwata, Kenneth K.
    Haley, John D.
    [J]. CLINICAL & EXPERIMENTAL METASTASIS, 2008, 25 (06) : 685 - 693
  • [2] Chen A, 2006, ONCOGENE, V25, P278, DOI [10.1038/sj.onc.1209019, 10.1038/sj.onc.1209573]
  • [3] Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis
    Conner, EA
    Lemmer, ER
    Omori, M
    Wirth, PJ
    Factor, VM
    Thorgeirsson, SS
    [J]. ONCOGENE, 2000, 19 (44) : 5054 - 5062
  • [4] The role of the EGFR signaling in tumor microenvironment
    De Luca, Antonella
    Carotenuto, Adele
    Rachiglio, Annamaria
    Gallo, Marianna
    Maiello, Monica R.
    Aldinucci, Donatella
    Pinto, Antonio
    Normanno, Nicola
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2008, 214 (03) : 559 - 567
  • [5] E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes
    Dicker, AJ
    Popa, C
    Dahler, AL
    Serewko, MM
    Hilditch-Maguire, PA
    Frazer, IH
    Saunders, NA
    [J]. ONCOGENE, 2000, 19 (25) : 2887 - 2894
  • [6] Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma
    Eymin, B
    Gazzeri, S
    Brambilla, C
    Brambilla, E
    [J]. ONCOGENE, 2001, 20 (14) : 1678 - 1687
  • [7] Differential regulation of noxa in normal Melanocytes and melanoma cells by proteasome inhibition:: Therapeutic implications
    Fernández, Y
    Verhaegen, M
    Miller, TP
    Rush, JL
    Steiner, P
    Opipari, AW
    Lowe, SW
    Soengas, MS
    [J]. CANCER RESEARCH, 2005, 65 (14) : 6294 - 6304
  • [8] E2F1 induces MRN foci formation and a cell cycle checkpoint response in human fibroblasts
    Frame, F. M.
    Rogoff, H. A.
    Pickering, M. T.
    Cress, W. D.
    Kowalik, T. F.
    [J]. ONCOGENE, 2006, 25 (23) : 3258 - 3266
  • [9] Apaf-1 is a mediator of E2F-1-induced apoptosis
    Furukawa, Y
    Nishimura, N
    Furukawa, Y
    Satoh, M
    Endo, H
    Iwase, S
    Yamada, H
    Matsuda, M
    Kano, Y
    Nakamura, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) : 39760 - 39768
  • [10] GINSBERG D, 2007, SCI STKE, V371, pPE4