Published in Cancer Detection and Prevention 2002; 26(6).

Transcriptional control of the RECK metastasis/angiogenesis suppressor gene

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

aInstituto de Química, Universidade de São Paulo, CP 26077, São Paulo 05513-970, SP, Brazil bDepartment of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan cDepartamento de Bioquímica, Faculdade de Odontologia de Bauru, Universidade de São Paulo, Bauru 17012-901, SP, Brazil

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.

KEY WORDS: Tumor suppressor gene, Metastasis, Angiogenesis, Transcriptional control, Sp1 transcription factor.