Transcriptional control of the RECK metastasis/angiogenesis suppressor gene

Regina Maki Sasahara, Sheila Maria Brochado, Chiaki Takahashi, Junseo Oh, Silvya Stuchi Maria-Engler, José Mauro Granjeiro, Makoto Noda, Mari Cleide Sogayar

    Research output: Contribution to journalArticlepeer-review

    51 Citations (Scopus)

    Abstract

    The RECK gene is widely expressed in normal human tissues but is downregulated in tumor cell lines and oncogenically transformed fibroblasts. RECK encodes a membrane-anchored glycoprotein that suppresses tumor invasion and angiogenesis by regulating matrix-metalloproteinases (MMP-2, MMP-9 and MT1-MMP). Understanding of the transcriptional regulation of tumor/metastasis suppressor genes constitutes a potent approach to the molecular basis of malignant transformation. In order to uncover the mechanisms of control of RECK gene expression, the RECK promoter has been cloned and characterized. One of the elements responsible for the Ras-mediated downregulation of mouse RECK gene is the Sp1 site, to which Sp1 and Sp3 factors bind. Other regulatory events, such as DNA methylation of the RECK promoter and histone acetylation/deacetylation have been studied to understand the underlying mechanisms of RECK expression. Understanding of the mechanisms which control RECK gene transcription may lead to the development of new strategies for cancer prevention and treatment.

    Original languageEnglish
    Pages (from-to)435-443
    Number of pages9
    JournalCancer Detection and Prevention
    Volume26
    Issue number6
    DOIs
    Publication statusPublished - 2002

    Bibliographical note

    Funding Information:
    We thank Zizi de Mendonça, Irenice Cairo da Silva, Sandra Regina Souza and Débora Cristina Costa for excellent technical support. RMS and SMB are supported by, respectively, a post-doctoral and a pre-doctoral fellowship from FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo). This work was supported by FAPESP, CNPq, PADCT-SBIO, CABBIO, FINEP, ICGEB, PRP-USP, Japanese Foundation for Cancer Research, Ministry of Education, Science, Sports and Culture and Technology Agency of the Japanese Government.

    Keywords

    • Angiogenesis
    • Metastasis
    • Sp1 transcription factor
    • Transcriptional control
    • Tumor suppressor gene

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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