Linked Life Data

21514422

Source:http://linkedlifedata.com/resource/pubmed/id/21514422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-25
pubmed:abstractText
Arsenic-induced Bowen's disease (As-BD), a cutaneous carcinoma in situ, is thought to arise from gene mutation and uncontrolled proliferation. However, how mitochondria regulate the arsenic-induced cell proliferation remains unclear. The aim of this study was to clarify whether arsenic interfered with mitochondrial biogenesis and function, leading to aberrant cell proliferation in As-BD. Skin biopsy samples from patients with As-BD and controls were stained for cytochrome c oxidase (Complex IV), measured for mitochondrial DNA (mtDNA) copy number and the expression levels of mitochondrial biogenesis-related genes, including peroxisome proliferator-activated receptor gamma coactivator-1? (PGC-1?), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (mtTFA). The results showed that expression of cytochrome c oxidase, mtTFA, NRF-1, and PGC-1? was increased in As-BD compared with in healthy subjects. Treatment of primary keratinocytes with arsenic at concentrations lower than 1.0 ?mol/L induced cell proliferation, along with enhanced mitochondrial biogenesis. Furthermore, we observed that the mitochondrial oxygen consumption rate and intracellular ATP level were increased in arsenic-treated keratinocytes. Blocking of mitochondrial function by oligomycin A (Complex V inhibitor) or knockdown of mtTFA by RNA interference abrogated arsenic-induced cell proliferation without affecting cyclin D1 expression. We concluded that mtTFA up-regulation, augmented mitochondrial biogenesis, and enhanced mitochondrial functions may contribute to arsenic-induced cell proliferation. Targeting mitochondrial biogenesis may help treat arsenical cancers at the stage of cell proliferation.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1525-2191
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2066-76
pubmed:meshHeading
pubmed-meshheading:21514422-Aged, pubmed-meshheading:21514422-Arsenic, pubmed-meshheading:21514422-Arsenic Poisoning, pubmed-meshheading:21514422-Blotting, Western, pubmed-meshheading:21514422-Bowen's Disease, pubmed-meshheading:21514422-Cell Proliferation, pubmed-meshheading:21514422-Cell Respiration, pubmed-meshheading:21514422-Cell Transformation, Neoplastic, pubmed-meshheading:21514422-DNA-Binding Proteins, pubmed-meshheading:21514422-Humans, pubmed-meshheading:21514422-Immunohistochemistry, pubmed-meshheading:21514422-Keratinocytes, pubmed-meshheading:21514422-Mitochondria, pubmed-meshheading:21514422-Mitochondrial Proteins, pubmed-meshheading:21514422-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21514422-Skin Neoplasms, pubmed-meshheading:21514422-Transcription Factors
pubmed:year
2011
pubmed:articleTitle
Aberrant cell proliferation by enhanced mitochondrial biogenesis via mtTFA in arsenical skin cancers.
pubmed:affiliation
Department of Dermatology, Graduate Institute of Medicine, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't