Aromatase expression is increased in <it>BRCA1 </it>mutation carriers
<p>Abstract</p> <p>Background</p> <p>Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of <it>BRCA1 </it>gene mutations had not been clearly understood. Of significance is the finding that BRCA1...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2009-05-01
|
Series: | BMC Cancer |
Online Access: | http://www.biomedcentral.com/1471-2407/9/148 |
_version_ | 1811285771360927744 |
---|---|
author | Chand Ashwini L Simpson Evan R Clyne Colin D |
author_facet | Chand Ashwini L Simpson Evan R Clyne Colin D |
author_sort | Chand Ashwini L |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of <it>BRCA1 </it>gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression <it>in vitro</it>. Our objective was to characterise aromatase gene <it>(CYP19A1) </it>and its promoter expression in breast adipose and ovarian tissue in <it>BRCA1 </it>mutation carriers and unaffected controls.</p> <p>Methods</p> <p>We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women.</p> <p>Results</p> <p>We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of <it>BRCA1 </it>mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts.</p> <p>Conclusion</p> <p>Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in <it>BRCA1 </it>mutation carriers.</p> |
first_indexed | 2024-04-13T02:48:57Z |
format | Article |
id | doaj.art-d57d2c578a2b44a9a78b525a2b3d94b4 |
institution | Directory Open Access Journal |
issn | 1471-2407 |
language | English |
last_indexed | 2024-04-13T02:48:57Z |
publishDate | 2009-05-01 |
publisher | BMC |
record_format | Article |
series | BMC Cancer |
spelling | doaj.art-d57d2c578a2b44a9a78b525a2b3d94b42022-12-22T03:05:54ZengBMCBMC Cancer1471-24072009-05-019114810.1186/1471-2407-9-148Aromatase expression is increased in <it>BRCA1 </it>mutation carriersChand Ashwini LSimpson Evan RClyne Colin D<p>Abstract</p> <p>Background</p> <p>Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of <it>BRCA1 </it>gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression <it>in vitro</it>. Our objective was to characterise aromatase gene <it>(CYP19A1) </it>and its promoter expression in breast adipose and ovarian tissue in <it>BRCA1 </it>mutation carriers and unaffected controls.</p> <p>Methods</p> <p>We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women.</p> <p>Results</p> <p>We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of <it>BRCA1 </it>mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts.</p> <p>Conclusion</p> <p>Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in <it>BRCA1 </it>mutation carriers.</p>http://www.biomedcentral.com/1471-2407/9/148 |
spellingShingle | Chand Ashwini L Simpson Evan R Clyne Colin D Aromatase expression is increased in <it>BRCA1 </it>mutation carriers BMC Cancer |
title | Aromatase expression is increased in <it>BRCA1 </it>mutation carriers |
title_full | Aromatase expression is increased in <it>BRCA1 </it>mutation carriers |
title_fullStr | Aromatase expression is increased in <it>BRCA1 </it>mutation carriers |
title_full_unstemmed | Aromatase expression is increased in <it>BRCA1 </it>mutation carriers |
title_short | Aromatase expression is increased in <it>BRCA1 </it>mutation carriers |
title_sort | aromatase expression is increased in it brca1 it mutation carriers |
url | http://www.biomedcentral.com/1471-2407/9/148 |
work_keys_str_mv | AT chandashwinil aromataseexpressionisincreasedinitbrca1itmutationcarriers AT simpsonevanr aromataseexpressionisincreasedinitbrca1itmutationcarriers AT clynecolind aromataseexpressionisincreasedinitbrca1itmutationcarriers |