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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
31
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pubmed:dateCreated |
2004-7-26
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pubmed:abstractText |
Recent studies have implicated heat shock proteins (HSP) and heat shock transcription factor 1 (HSF1) in tumor progression. We have examined the role of HSF1 in the malignant phenotype of PC-3 prostate carcinoma cells. We have developed a dominant negative construct of HSF1 that antagonizes transcription from HSP promoters and results in the depletion of intracellular HSP 70. Our studies indicate that expression of DN-HSF1 dramatically alters the DNA content of PC-3 cells (derived from p53 null prostatic carcinoma) and inhibits aneuploidy in these cells. This effect is due to prolonged expression of DN-HSF1, and transient expression of the dominant negative factor from an inducible promoter failed to cause the effect. Inhibition of aneuploidy in p53 null PC-3 cells by DN-HSF1 expression was recapitulated by expression within the cells of wild type p53. Furthermore, cells expressing DN-HSF1 showed a profound inhibition in the development of aneuploidy when exposed to chemical agents that disrupt the mitotic spindle and prevent progression through metaphase. Inhibition of aneuploidy in PC-3 cells expressing DN-HSF1 was associated with delayed breakdown of cyclin B1 compared with controls, consistent with a role for wild type HSF1 in the regulation of cyclin B1 degradation, a key step in the control of mitosis. Our experiments therefore demonstrate that HSF1 plays a functional role in cancer cells under nonstress conditions and influences cell cycle behavior and progression through mitosis and promotes the development of the aneuploid state.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/CCNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Demecolcine,
http://linkedlifedata.com/resource/pubmed/chemical/HSP72 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/heat shock transcription factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
32651-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15152009-Aneuploidy,
pubmed-meshheading:15152009-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:15152009-Cell Cycle,
pubmed-meshheading:15152009-Cell Division,
pubmed-meshheading:15152009-Cell Line,
pubmed-meshheading:15152009-Cell Line, Tumor,
pubmed-meshheading:15152009-Cells, Cultured,
pubmed-meshheading:15152009-Cyclin B,
pubmed-meshheading:15152009-Cyclin B1,
pubmed-meshheading:15152009-DNA,
pubmed-meshheading:15152009-DNA-Binding Proteins,
pubmed-meshheading:15152009-Demecolcine,
pubmed-meshheading:15152009-Dose-Response Relationship, Drug,
pubmed-meshheading:15152009-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15152009-G0 Phase,
pubmed-meshheading:15152009-Genes, Dominant,
pubmed-meshheading:15152009-Genes, Reporter,
pubmed-meshheading:15152009-Genes, p53,
pubmed-meshheading:15152009-Genetic Vectors,
pubmed-meshheading:15152009-HSP72 Heat-Shock Proteins,
pubmed-meshheading:15152009-Heat-Shock Proteins,
pubmed-meshheading:15152009-Humans,
pubmed-meshheading:15152009-Immunoblotting,
pubmed-meshheading:15152009-Luciferases,
pubmed-meshheading:15152009-Male,
pubmed-meshheading:15152009-Mitosis,
pubmed-meshheading:15152009-Mutation,
pubmed-meshheading:15152009-Phenotype,
pubmed-meshheading:15152009-Ploidies,
pubmed-meshheading:15152009-Promoter Regions, Genetic,
pubmed-meshheading:15152009-Prostatic Neoplasms,
pubmed-meshheading:15152009-Protein Structure, Tertiary,
pubmed-meshheading:15152009-Spectrometry, Fluorescence,
pubmed-meshheading:15152009-Transcription Factors,
pubmed-meshheading:15152009-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Expression of a dominant negative heat shock factor-1 construct inhibits aneuploidy in prostate carcinoma cells.
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pubmed:affiliation |
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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