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    Epigenetic silencing of BRCA1 and maspin in sporadic breast cancer

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    Author
    Rice, Judd Christopher
    Issue Date
    2000
    Keywords
    Biology, Molecular.
    Biology, Genetics.
    Health Sciences, Oncology.
    Advisor
    Futscher, Bernard W.
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The RNA expression of the tumor suppressor genes BRCA1 and maspin are frequently decreased or lost in sporadic breast cancer. We hypothesized that inactivation of these genes was due to aberrant epigenetic silencing at the level of gene transcription. In this study we show that aberrant cytosine methylation of the BRCA1 and maspin CpG island promoters is a common event in the inactivation of these genes in sporadic breast cancer cell lines. Furthermore, we show that the methylation-associated inactivation of BRCA1 occurs in 15-30% of sporadic breast cancer patient specimens and our data suggests that the methylation-associated inactivation of maspin occurs in ∼70% of advanced sporadic breast cancers. Additional studies indicate that the methylation associated inactivation of these genes is coincident with the repressive epigenetic events of histone hypoacetylation and chromatin condensation. These data suggest that aberrant cytosine methylation, histone hypoacetylation and chromatin condensation act together in the BRCA1 and maspin promoters to inactivate their transcription, thereby, contributing to the progression of sporadic breast cancer.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Pharmacology & Toxicology
    Degree Grantor
    University of Arizona
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