Document Detail


The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells.
MedLine Citation:
PMID:  15897892     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple copies in T-cell maligancy (MCT-1) is a putative oncogene initially identified in a human T-cell lymphoma. Forced expression of MCT-1 has recently been shown to induce cell transformation and proliferation, as well as to activate survival-related PI-3K/AKT pathways protecting cells from apoptosis. MCT-1 protein is stabilized in response to DNA damage. The impact of MCT-1 overexpression on DNA damage response remains unknown. Here, we show that MCT-1 deregulates cell cycle checkpoints. The phosphorylation of genomic stabilizers H2AX and NBS1 are enhanced in MCT-1-overexpressing cells. Forced expression of MCT-1 significantly increases the number of DNA damage-induced foci involving gamma-H2AX and 53BP1. In MCT-1-overexpressing cells, the proportion of S-phase cell population is preferentially increased after exposure to gamma-irradiation compared to controls. Knockdown of endogenous MCT-1 using an siRNA approach attenuates the H2AX phosphorylation and the G1/S checkpoint defect. Furthermore, MCT-1 is capable of transforming immortalized human mammary epithelial cells and promoting genomic instability. These data shed light on the role of MCT-1 in the cellular response to DNA damage and its involvement in malignant transformation.
Authors:
Hsin-Ling Hsu; Bo Shi; Ronald B Gartenhaus
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-22     Completed Date:  2005-09-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4956-64     Citation Subset:  IM    
Affiliation:
Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine and the Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Breast / cytology*
Breast Neoplasms
Cell Cycle / physiology*
Cell Cycle Proteins / metabolism*
Cell Line, Tumor
Cell Transformation, Neoplastic*
DNA Damage
DNA Primers
Epithelial Cells / cytology*,  pathology
Female
Humans
Lymphoma, T-Cell / genetics
Oncogene Proteins / metabolism,  physiology*
Oncogenes*
Plasmids
RNA Interference
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA Primers; 0/MCTS1 protein, human; 0/Oncogene Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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