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.
Bibliographical noteFunding 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.
- Sp1 transcription factor
- Transcriptional control
- Tumor suppressor gene
ASJC Scopus subject areas
- Cancer Research