Epigenetic silencing of BRCA1 and maspin in sporadic breast cancer
| dc.contributor.advisor | Futscher, Bernard W. | en_US |
| dc.contributor.author | Rice, Judd Christopher | |
| dc.creator | Rice, Judd Christopher | en_US |
| dc.date.accessioned | 2013-05-09T09:35:24Z | |
| dc.date.available | 2013-05-09T09:35:24Z | |
| dc.date.issued | 2000 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10150/289142 | |
| dc.description.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. | |
| dc.language.iso | en_US | en_US |
| dc.publisher | The University of Arizona. | en_US |
| dc.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. | en_US |
| dc.subject | Biology, Molecular. | en_US |
| dc.subject | Biology, Genetics. | en_US |
| dc.subject | Health Sciences, Oncology. | en_US |
| dc.title | Epigenetic silencing of BRCA1 and maspin in sporadic breast cancer | en_US |
| dc.type | text | en_US |
| dc.type | Dissertation-Reproduction (electronic) | en_US |
| thesis.degree.grantor | University of Arizona | en_US |
| thesis.degree.level | doctoral | en_US |
| dc.identifier.proquest | 9972095 | en_US |
| thesis.degree.discipline | Graduate College | en_US |
| thesis.degree.discipline | Pharmacology & Toxicology | en_US |
| thesis.degree.name | Ph.D. | en_US |
| dc.description.note | This item was digitized from a paper original and/or a microfilm copy. If you need higher-resolution images for any content in this item, please contact us at repository@u.library.arizona.edu. | |
| dc.identifier.bibrecord | .b40639502 | en_US |
| dc.description.admin-note | Original file replaced with corrected file April 2023. | |
| refterms.dateFOA | 2018-06-16T11:02:10Z | |
| html.description.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. |
