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ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers

Aromatase, the rate-limiting enzyme in estrogen synthesis, is expressed in the ovaries of premenopausal, the placentas of pregnant women, and adipose tissue and skin cells in postmenopausal women, although to a lesser extent than in the ovaries. The direct mechanism of controlling breast cancer is t...

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Autores principales: Cubbedge, Chandler, Perkins, Edward, Burak, William, Bose, Himangshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627972/
http://dx.doi.org/10.1210/jendso/bvac150.1794
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author Cubbedge, Chandler
Perkins, Edward
Burak, William
Bose, Himangshu
author_facet Cubbedge, Chandler
Perkins, Edward
Burak, William
Bose, Himangshu
author_sort Cubbedge, Chandler
collection PubMed
description Aromatase, the rate-limiting enzyme in estrogen synthesis, is expressed in the ovaries of premenopausal, the placentas of pregnant women, and adipose tissue and skin cells in postmenopausal women, although to a lesser extent than in the ovaries. The direct mechanism of controlling breast cancer is to reduce estrogen synthesis by interfering with its production, via ovarian ablation in premenopausal women and use of aromatase inhibitors or inactivators. However, the latter results in drug resistance, making them ineffective for future treatment. In our laboratory, we identified a 22-kDa protein from human breast tissue, Aromatase Interacting Partner in Breast (AIPB), that interacts with aromatase. Western Blotting of the unaffected (nontumorigenic MCF-12A) and tumorigenic (MCF-7 ER+/PR+/Her2-) breast tissues as well as PCR amplification with the AIPB specific primers of the nontumorigenic and tumorigenic cells showed AIPB expression is maximum with the unaffected breast tissue but reduced in ER+/PR+/Her2- tumors. To confirm AIPB's regulatory role, we developed a conditional expression of AIPB by stably selecting with puromycin from MCF-7 cells and thus regulating AIPB expression under a tetracycline promoter. On addition of doxycycline followed by PCR amplification, the AIPB expression was enormously higher than the uninduced cells under identical condition. The estrogenic effect of the stable cells was reduced significantly compared to MCF-7 cells. In summary, our preliminary results suggest AIPB to be a potential biomarker with a potential for cell therapy-mediated decrease of estradiol in ER+/PR+/Her2- tumorigenic breast tissues. Presentation: No date and time listed
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spelling pubmed-96279722022-11-04 ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers Cubbedge, Chandler Perkins, Edward Burak, William Bose, Himangshu J Endocr Soc Tumor Biology Aromatase, the rate-limiting enzyme in estrogen synthesis, is expressed in the ovaries of premenopausal, the placentas of pregnant women, and adipose tissue and skin cells in postmenopausal women, although to a lesser extent than in the ovaries. The direct mechanism of controlling breast cancer is to reduce estrogen synthesis by interfering with its production, via ovarian ablation in premenopausal women and use of aromatase inhibitors or inactivators. However, the latter results in drug resistance, making them ineffective for future treatment. In our laboratory, we identified a 22-kDa protein from human breast tissue, Aromatase Interacting Partner in Breast (AIPB), that interacts with aromatase. Western Blotting of the unaffected (nontumorigenic MCF-12A) and tumorigenic (MCF-7 ER+/PR+/Her2-) breast tissues as well as PCR amplification with the AIPB specific primers of the nontumorigenic and tumorigenic cells showed AIPB expression is maximum with the unaffected breast tissue but reduced in ER+/PR+/Her2- tumors. To confirm AIPB's regulatory role, we developed a conditional expression of AIPB by stably selecting with puromycin from MCF-7 cells and thus regulating AIPB expression under a tetracycline promoter. On addition of doxycycline followed by PCR amplification, the AIPB expression was enormously higher than the uninduced cells under identical condition. The estrogenic effect of the stable cells was reduced significantly compared to MCF-7 cells. In summary, our preliminary results suggest AIPB to be a potential biomarker with a potential for cell therapy-mediated decrease of estradiol in ER+/PR+/Her2- tumorigenic breast tissues. Presentation: No date and time listed Oxford University Press 2022-11-01 /pmc/articles/PMC9627972/ http://dx.doi.org/10.1210/jendso/bvac150.1794 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Tumor Biology
Cubbedge, Chandler
Perkins, Edward
Burak, William
Bose, Himangshu
ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers
title ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers
title_full ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers
title_fullStr ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers
title_full_unstemmed ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers
title_short ODP539 AIPB is a Biomarker for ER+/PR+/Her2- Breast Cancers
title_sort odp539 aipb is a biomarker for er+/pr+/her2- breast cancers
topic Tumor Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627972/
http://dx.doi.org/10.1210/jendso/bvac150.1794
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