Abstract |
In this report, we describe the mechanism of TGF-beta receptor type I (RI) repression in the GEO human colon carcinoma cells. Treatment of GEO cells with the DNA methyltransferase inhibitor, 5 azacytidine induced RI expression and restored TGF-beta response. A stably transfected RI promoter-reporter construct (RI-Luc) expressed higher activity in the 5 aza C treated GEO cells, suggesting the activation of a transactivator for RI transcription. Gel shift analysis indicated enhanced binding of proteins from the 5 aza C treated nuclear extracts to radiolabeled Sp1 oligonucleotides specifically contained in the RI promoter. Protein stability studies after cyclohexamide treatment suggested an increase in the Sp1 protein stability from the 5 aza C treated GEO cells. Further, transfection of Sp1 cDNA into untreated GEO control cells increased RI promoter activity and thus induced RI expression. 5 aza C mediated Sp1 expression in Sp1 deficient GEO colon and MCF-7 breast cancer cells also enhanced the activity of several other Sp1 dependent promoters such as TGF-beta receptor type II (RII), Cyclin A and p21/waf1/cip1. These results indicate that restoration of Sp1 in several different types of Sp1 deficient cells leads to enhanced activation of a wide range of Sp1 dependent promoters.
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Authors | S Periyasamy, S Ammanamanchi, M P Tillekeratne, M G Brattain |
Journal | Oncogene
(Oncogene)
Vol. 19
Issue 40
Pg. 4660-7
(Sep 21 2000)
ISSN: 0950-9232 [Print] England |
PMID | 11030155
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimetabolites, Antineoplastic
- CDKN1A protein, human
- Cyclin A
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
- Enzyme Inhibitors
- Neoplasm Proteins
- Receptors, Transforming Growth Factor beta
- Recombinant Fusion Proteins
- Sp1 Transcription Factor
- DNA (Cytosine-5-)-Methyltransferases
- Protein Serine-Threonine Kinases
- Activin Receptors, Type I
- Receptor, Transforming Growth Factor-beta Type I
- Receptor, Transforming Growth Factor-beta Type II
- Azacitidine
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Topics |
- Activin Receptors, Type I
- Adenocarcinoma
(genetics, metabolism, pathology)
- Antimetabolites, Antineoplastic
(pharmacology)
- Azacitidine
(pharmacology)
- Breast Neoplasms
(genetics, metabolism, pathology)
- Colonic Neoplasms
(genetics, metabolism, pathology)
- Cyclin A
(biosynthesis, genetics)
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
(biosynthesis, genetics)
- DNA (Cytosine-5-)-Methyltransferases
(antagonists & inhibitors)
- DNA Methylation
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Neoplasm Proteins
(biosynthesis, deficiency, genetics, physiology)
- Promoter Regions, Genetic
(genetics)
- Protein Serine-Threonine Kinases
(biosynthesis, genetics)
- Receptor, Transforming Growth Factor-beta Type I
- Receptor, Transforming Growth Factor-beta Type II
- Receptors, Transforming Growth Factor beta
(biosynthesis, genetics)
- Recombinant Fusion Proteins
(physiology)
- Sp1 Transcription Factor
(deficiency, physiology)
- Transcriptional Activation
- Transfection
- Tumor Cells, Cultured
(drug effects, metabolism)
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