| 1. |
- Gururaj, Anupama E, et al.
(författare)
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Breast cancer-amplified sequence 3, a target of metastasis-associated protein 1, contributes to tamoxifen resistance in premenopausal patients with breast cancer
- 2006
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Ingår i: Cell Cycle. - 1551-4005. ; 5:13, s. 1407-1410
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Tidskriftsartikel (refereegranskat)abstract
- Lysine acetylation occurs in many protein targets, including core histones, transcription factors, and other proteins. Metastasis-associated protein 1 (MTA1) is implicated in the progression and metastasis of various epithelial tumors. Because MTA1 functions as a transcriptional coregulator, much of its role in cancer promoting processes are likely to involve its ability to regulate the transcription of downstream target genes that encode effector proteins. We recently showed that MTA1 could be post-translationally modified by acetylation, which modulates its function as a coregulator molecule. We also defined a chromatin target of MTA1, namely, breast cancer-amplified sequence 3 (BCAS3), in the context of which MTA1 behaves as a transcriptional coactivator in breast cancer cells. Because the phenotypic effect of BCAS3 overexpression in tumors has not been defined, we investigated the consequence of increased expression of BCAS3 in human breast tumors. Here, we report that BCAS3 overexpression in hormone receptor-positive premenopausal breast cancer seemed to be associated with impaired responses to tamoxifen. Our findings have implications for endocrine therapy.
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| 2. |
- Ohshiro, Kazufumi, et al.
(författare)
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Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator.
- 2010
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Ingår i: EMBO reports. - : EMBO. - 1469-3178 .- 1469-221X. ; 11:9, s. 691-7
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Tidskriftsartikel (refereegranskat)abstract
- High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of Galphai2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the Galphai2 regulatory element and consequently for the repression of Galphai2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time--to the best of our knowledge--evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product.
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