Linked Life Data

15897899

Source:http://linkedlifedata.com/resource/pubmed/id/15897899

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2005-7-22
pubmed:abstractText
We previously reported that 17-beta-estradiol (E2)-induced mitochondrial reactive oxygen species (mtROS) act as signaling molecules. The purpose of this study was to investigate the effects of E2-induced mtROS on cell cycle progression. E2-induced cell growth was reduced by antioxidants N-acetyl-L-cysteine (NAC), catalase, and the glutathione peroxidase mimic ebselen. Flow cytometry showed that mitochondrial blockers of protein synthesis (chloramphenicol), transcription and replication (ethidium bromide), and function (rotenone, rhodamine 6G) blocked E2-induced G1 to S transition. Reduction of E2-induced DNA synthesis in the presence of mitochondrial blockers occurred without influencing the level of ATP. Additionally, the mitochondrial blockers inhibited the E2-induced expression of early cell cycle genes such as cyclins D1, D3, E1, E2, and B2. NAC or rotenone reduced E2-induced cyclin D1 expression. Furthermore, E2-induced binding of AP-1 and CREB to the TRE and CRE response sequences, respectively, in the promoter of cyclin D1 was inhibited by NAC or rotenone. In addition, E2-induced expression of PCNA, PRC1, and bcl-2 were inhibited by mitochondrial blockers. These data indicate that E2-induced mtROS are involved in the regulation of early G1-phase progression. Since neither antioxidants nor mitochondrial blockers used in this study are reported to bind the estrogen receptor (ER), our findings suggest that E2-induced mtROS modulates G1 to S transition and some of the early G1 genes through a nongenomic, ER-independent signaling pathway. Thus, our results suggest (1) a new paradigm that estrogen-induced mitochondrial oxidants control the early stage of cell cycle progression and (2) provide the basis for the discovery of novel antioxidant-based drugs or antioxidant gene therapies for the prevention and treatment of estrogen-dependent breast cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4883-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15897899-Base Sequence, pubmed-meshheading:15897899-Breast Neoplasms, pubmed-meshheading:15897899-Cell Cycle, pubmed-meshheading:15897899-Cell Division, pubmed-meshheading:15897899-Cell Line, Tumor, pubmed-meshheading:15897899-Chloramphenicol, pubmed-meshheading:15897899-DNA Primers, pubmed-meshheading:15897899-Estradiol, pubmed-meshheading:15897899-Ethidium, pubmed-meshheading:15897899-G1 Phase, pubmed-meshheading:15897899-Humans, pubmed-meshheading:15897899-Mitochondria, pubmed-meshheading:15897899-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15897899-Oxidants, pubmed-meshheading:15897899-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15897899-Rotenone, pubmed-meshheading:15897899-S Phase, pubmed-meshheading:15897899-Signal Transduction
pubmed:year
2005
pubmed:articleTitle
Estrogen-induced G1/S transition of G0-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling.
pubmed:affiliation
Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural