Transcriptional control of the RECK metastasis/angiogenesis suppressor gene.
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.
Sasahara
Regina Maki
RM
Instituto de Química, Universidade de São Paulo, CP 26077, São Paulo 05513-970, SP, Brazil.
Brochado
Sheila Maria
SM
Takahashi
Chiaki
C
Oh
Junseo
J
Maria-Engler
Silvya Stuchi
SS
Granjeiro
José Mauro
JM
Noda
Makoto
M
Sogayar
Mari Cleide
MC
D000107:Acetylation; D000818:Animals; D019175:DNA Methylation; D015536:Down-Regulation; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D011905:Genes, ras / Q000502:physiology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology; D014158:Transcription, Genetic
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; C492025:Reck protein, mouse; D016329:Sp1 Transcription Factor; D020782:Matrix Metalloproteinases; D006655:Histone Deacetylases