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Emerging roles of MTA family members in human cancers
- Source :
- Seminars in Oncology. 30:30-37
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Metastasis-associated genes (MTAs) represent a rapidly growing novel gene family. At present, there are three different known genes (MTA1, MTA2, and MTA3) and six reported isoforms (MTA1, MTA1s, MTA1-ZG29p, MTA2, MTA3, MTA3L). MTA1, MTA2, and MTA3 are components of the nucleosome remodeling and deacetylation complex, which is associated with adenosine triphosphate-dependent chromatin remodeling and transcriptional regulation. MTA proteins, as a part of the NuRD complex (nuclear remodeling and deacetylation complex), are thought to modulate transcription by influencing the status of chromatin remodeling. MTA1 overexpression is closely correlated with an aggressive course in several human carcinomas. Recent studies have shown that growth factor stimulation of breast cancer cells induces the expression of MTA1 and its interaction with and repression of the estrogen receptor (ER) transactivation function, leading to enhanced anchorage-independent growth in vitro and hormone independence. Furthermore, the status of the ER pathway modulates the expression of MTA3 as well as epithelial-to-mesenchymal transition in human breast tumors. MTA1 expression is not restricted to tumors; however, several normal mouse tissues and organs also express substantial levels of MTA1. Thus, MTA1 may play a role in both the physiologic and the pathologic states of cells. In Caenorhabditis elegans, MTA1-like genes regulate cell polarity, migration, embryonic patterning, and vulva development. In addition, two naturally occurring variants of MTA1, MTA1-ZG29p, and MTA1s have also been identified. ZG29p is an N-terminal truncated form of MTA1 and is present in the zymogen granules of the pancreas. In contrast, MTA1s is the C-terminal truncated form present in the cytoplasm. MTA1s binds and inhibits the nuclear functions of the ER by sequestering it to cytoplasm, stimulating the mitogen-activated protein kinase pathway. Furthermore, breast tumors with no or low ER in the nucleus exhibit elevated levels of MTA1s and cytoplasmic subcellular localization of the ER. This article reviews the current status of MTA biochemistry and its implications for tumor biology.
- Subjects :
- Protein Conformation
Molecular Sequence Data
Gene Expression
Estrogen receptor
Breast Neoplasms
Biology
Histone Deacetylases
Chromatin remodeling
Transactivation
Transcriptional regulation
Animals
Humans
Amino Acid Sequence
Neoplasm Metastasis
Caenorhabditis elegans Proteins
MTA2
Proteins
Hematology
Subcellular localization
Zymogen granule
Mi-2/NuRD complex
Neoplasm Proteins
DNA-Binding Proteins
Repressor Proteins
Gene Expression Regulation
Receptors, Estrogen
Oncology
Trans-Activators
Cancer research
Carrier Proteins
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Transcription Factors
Subjects
Details
- ISSN :
- 00937754
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Seminars in Oncology
- Accession number :
- edsair.doi.dedup.....3a4619c2b4c0d087ed3b9169775f8eee