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3300 Progesterone receptor alters lipid biology in luminal breast cancer
OBJECTIVES/SPECIFIC AIMS: These studies seek to evaluate hormonal regulation of luminal breast cancer lipid metabolism and to identify targetable progesterone-mediated changes in lipid biology that contribute to therapeutic resistance in breast cancer. METHODS/STUDY POPULATION: Established and patie...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cambridge University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799335/ http://dx.doi.org/10.1017/cts.2019.46 |
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author | Ward, Ashley Vanessa Matthews, Shawna B. Sartorius, Carol A. |
author_facet | Ward, Ashley Vanessa Matthews, Shawna B. Sartorius, Carol A. |
author_sort | Ward, Ashley Vanessa |
collection | PubMed |
description | OBJECTIVES/SPECIFIC AIMS: These studies seek to evaluate hormonal regulation of luminal breast cancer lipid metabolism and to identify targetable progesterone-mediated changes in lipid biology that contribute to therapeutic resistance in breast cancer. METHODS/STUDY POPULATION: Established and patient-derived luminal breast cancer cell lines, which express ER and PR, were used for this study. RNA transcript and protein expression levels were evaluated by qRT-PCR and immunoblot, respectively. Broad scale lipidomics of progesterone-treated cells was conducted via ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) through the UCD Skaggs School of Pharmacy Mass Spectrometry Core. RESULTS/ANTICIPATED RESULTS: Data mining of previously published microarray data of CK5+ and CK5− syngeneic cancer sublines revealed that CK5+ cells have increased expression of lipid processing genes, including LPL and PPARG. As progestin treatment induces a subpopulation of cells to turn on CK5 expression in luminal breast cancers, UHPLC-MS-based lipidomics analysis will expose whether modulation of the lipid landscape occurs in all cells with progesterone treatment, or whether this phenomenon is heightened specifically in CK5+ cells. I also expect that ER+ breast cancers with progestin induced-altered lipid content, such as lipid droplet formation, will evade therapy-induced death. DISCUSSION/SIGNIFICANCE OF IMPACT: There are numerous approved and developmental therapeutics targeting lipid biology. By determining if progestins alter lipid metabolic genes specifically in CK5+ CSCs, which are endocrine resistant, strategies may be devised to target these resistant cells using combination therapy in conjunction with existing therapies to prevent tumor recurrence. |
format | Online Article Text |
id | pubmed-6799335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67993352019-10-28 3300 Progesterone receptor alters lipid biology in luminal breast cancer Ward, Ashley Vanessa Matthews, Shawna B. Sartorius, Carol A. J Clin Transl Sci Basic/Translational Science/Team Science OBJECTIVES/SPECIFIC AIMS: These studies seek to evaluate hormonal regulation of luminal breast cancer lipid metabolism and to identify targetable progesterone-mediated changes in lipid biology that contribute to therapeutic resistance in breast cancer. METHODS/STUDY POPULATION: Established and patient-derived luminal breast cancer cell lines, which express ER and PR, were used for this study. RNA transcript and protein expression levels were evaluated by qRT-PCR and immunoblot, respectively. Broad scale lipidomics of progesterone-treated cells was conducted via ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) through the UCD Skaggs School of Pharmacy Mass Spectrometry Core. RESULTS/ANTICIPATED RESULTS: Data mining of previously published microarray data of CK5+ and CK5− syngeneic cancer sublines revealed that CK5+ cells have increased expression of lipid processing genes, including LPL and PPARG. As progestin treatment induces a subpopulation of cells to turn on CK5 expression in luminal breast cancers, UHPLC-MS-based lipidomics analysis will expose whether modulation of the lipid landscape occurs in all cells with progesterone treatment, or whether this phenomenon is heightened specifically in CK5+ cells. I also expect that ER+ breast cancers with progestin induced-altered lipid content, such as lipid droplet formation, will evade therapy-induced death. DISCUSSION/SIGNIFICANCE OF IMPACT: There are numerous approved and developmental therapeutics targeting lipid biology. By determining if progestins alter lipid metabolic genes specifically in CK5+ CSCs, which are endocrine resistant, strategies may be devised to target these resistant cells using combination therapy in conjunction with existing therapies to prevent tumor recurrence. Cambridge University Press 2019-03-27 /pmc/articles/PMC6799335/ http://dx.doi.org/10.1017/cts.2019.46 Text en © The Association for Clinical and Translational Science 2019 http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (http://creativecommons.org/licenses/by-ncnd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work. |
spellingShingle | Basic/Translational Science/Team Science Ward, Ashley Vanessa Matthews, Shawna B. Sartorius, Carol A. 3300 Progesterone receptor alters lipid biology in luminal breast cancer |
title | 3300 Progesterone receptor alters lipid biology in luminal breast cancer |
title_full | 3300 Progesterone receptor alters lipid biology in luminal breast cancer |
title_fullStr | 3300 Progesterone receptor alters lipid biology in luminal breast cancer |
title_full_unstemmed | 3300 Progesterone receptor alters lipid biology in luminal breast cancer |
title_short | 3300 Progesterone receptor alters lipid biology in luminal breast cancer |
title_sort | 3300 progesterone receptor alters lipid biology in luminal breast cancer |
topic | Basic/Translational Science/Team Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799335/ http://dx.doi.org/10.1017/cts.2019.46 |
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