Source:http://linkedlifedata.com/resource/pubmed/id/20862710
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2010-11-30
|
| pubmed:abstractText |
Arsenic trioxide (ATO) is a first-line anti-cancer agent for acute promyelocytic leukemia, and induces apoptosis in other solid cancer cell lines including breast cancer cells. However, as with arsenites found in drinking water and used as raw materials for wood preservatives, insecticides, and herbicides, low doses of ATO can induce carcinogenesis after long-term exposure. At 24?h after exposure, ATO (0.01-1 µM) significantly increased cell proliferation and promoted cell cycle progression from the G1 to S/G2 phases in the non-tumorigenic MCF10A breast epithelial cell line. The expression of 14 out of 96 cell-cycle-associated genes significantly increased, and seven of these genes including cell division cycle 6 (CDC6) and cyclin D1 (CCND1) were closely related to cell cycle progression from G1 to S phase. Low-dose ATO steadily increased gene transcript and protein levels of both CDC6 and cyclin D1 in a dose- and time-dependent manner. Low-dose ATO produced reactive oxygen species (ROS), and activated the p38 MAPK, Akt, and ERK1/2 pathways at different time points within 60 min. Small molecular inhibitors and siRNAs inhibiting the activation of p38 MAPK, Akt, and ERK1/2 decreased the ATO-increased expression of CDC6 protein. Inhibiting the activation of Akt and ERK1/2, but not p38 MAPK, decreased the ATO-induced expression of cyclin D1 protein. This study reports for the first time that p38 MAPK/Akt/ERK1/2 activation is required for the protein stabilization of CDC6 in addition to cyclin D1 in ATO-induced cell proliferation and cell cycle modulation from G1 to S phase.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arsenicals,
http://linkedlifedata.com/resource/pubmed/chemical/CDC6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxides,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/arsenic trioxide,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
1097-4644
|
| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2010 Wiley-Liss, Inc.
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
111
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1546-55
|
| pubmed:meshHeading |
pubmed-meshheading:20862710-Arsenicals,
pubmed-meshheading:20862710-Blotting, Western,
pubmed-meshheading:20862710-Cell Cycle,
pubmed-meshheading:20862710-Cell Cycle Proteins,
pubmed-meshheading:20862710-Cell Line, Tumor,
pubmed-meshheading:20862710-Cell Proliferation,
pubmed-meshheading:20862710-Cyclin D1,
pubmed-meshheading:20862710-Flow Cytometry,
pubmed-meshheading:20862710-Humans,
pubmed-meshheading:20862710-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:20862710-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:20862710-Nuclear Proteins,
pubmed-meshheading:20862710-Oxides,
pubmed-meshheading:20862710-Protein Stability,
pubmed-meshheading:20862710-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20862710-Reactive Oxygen Species,
pubmed-meshheading:20862710-p38 Mitogen-Activated Protein Kinases
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Activation of the p38 MAPK/Akt/ERK1/2 signal pathways is required for the protein stabilization of CDC6 and cyclin D1 in low-dose arsenite-induced cell proliferation.
|
| pubmed:affiliation |
Maine Institute for Human Genetics and Health, 246 Sylvan Road, Maine 04401, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|