التفاصيل البيبلوغرافية
| العنوان: |
Metastasis-associated Protein 1/Histone Deacetylase 4-Nucleosome Remodeling and Deacetylase Complex Regulates Phosphatase and Tensin Homolog Gene Expression and Function. |
| المؤلفون: |
Reddy, Sirigiri Divijendra Natha1, Pakala, Suresh B.1, Molli, Poonam R.1, Sahni, Neil1, Karanam, Narasimha Kumar1, Mudvari, Prakriti1, Kumar, Rakesh1 bcmrxk@gwu.edu |
| المصدر: |
Journal of Biological Chemistry. 8/10/2012, Vol. 287 Issue 33, p27843-27850. 8p. |
| مصطلحات موضوعية: |
*METASTASIS, *CANCER invasiveness, *BREAST cancer, *GENE expression, *TUMOR suppressor genes |
| مستخلص: |
Metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with malignant phenotypic changes contributing to morbidity in the associated diseases. Here we discovered for the first time that MTA1, a master chromatin modifier, transcriptionally represses the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, by recruiting class II histone deacetylase 4 (HDAC4) along with the transcription factor Yin-Yang 1 (YY1) onto the PTEN promoter. We also found evidence of an inverse correlation between the expression levels of MTA1 and PTEN in physiologically relevant breast cancer microarray datasets.Wefound that MTA1 up-regulation leads to a decreased expression of PTEN protein and stimulation of PI3K as well as phosphorylation of its signaling targets. Accordingly, selective down-regulation of MTA1 in breast cancer cells increases PTEN expression and inhibits stimulation of the PI3K/AKT signaling. Collectively, these findings provide a mechanistic role for MTA1 in transcriptional repression of PTEN, leading to modulation of the resulting signaling pathways. [ABSTRACT FROM AUTHOR] |
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