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LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women
BACKGROUND: Triple-negative breast cancer (TNBC) is more prevalent in African and African American (AA) women compared to European American (EA) women. African and AA women diagnosed with TNBC experience high frequencies of metastases and less favorable outcomes. Emerging evidence indicates that thi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304259/ https://www.ncbi.nlm.nih.gov/pubmed/30588086 http://dx.doi.org/10.2147/BCTT.S185960 |
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author | Torres-Luquis, Odalys Madden, Krystal N’dri, N’sanh MR Berg, Richard Olopade, Olufunmilayo F Ngwa, Wilfred Abuidris, Dafalla Mittal, Suresh Lyn-Cook, Beverly Mohammed, Sulma I |
author_facet | Torres-Luquis, Odalys Madden, Krystal N’dri, N’sanh MR Berg, Richard Olopade, Olufunmilayo F Ngwa, Wilfred Abuidris, Dafalla Mittal, Suresh Lyn-Cook, Beverly Mohammed, Sulma I |
author_sort | Torres-Luquis, Odalys |
collection | PubMed |
description | BACKGROUND: Triple-negative breast cancer (TNBC) is more prevalent in African and African American (AA) women compared to European American (EA) women. African and AA women diagnosed with TNBC experience high frequencies of metastases and less favorable outcomes. Emerging evidence indicates that this disparity may in fact be the result of the uniquely aggressive biology of African and AA disease. PURPOSE: To understand the reasons for TNBC in AA aggressive biology, we designed the present study to examine the proteomic profiles of TNBC and luminal A (LA) breast cancer within and across patients’ racial demographic groups in order to identify proteins or molecular pathways altered in TNBC that offer some explanation for its aggressiveness and potential targets for treatment. MATERIALS AND METHODS: Proteomic profiles of TNBC, LA tumors, and their adjacent normal tissues from AA and EA women were obtained using 2-dimensional gel electrophoresis and bioinformatics, and differentially expressed proteins were validated by Western blot and immunohistochemistry. Our data showed that a number of proteins have significantly altered in expression in LA tumors compared to TNBC, both within and across patients’ racial demographic groups. The differentially overexpressed proteins in TNBC (compared to LA) of AA samples were distinct from those in TNBC (compared to LA) of EA women samples. Among the signaling pathways altered in AA TNBC compared to EA TNBC are innate immune signaling, calpain protease, and pyrimidine de novo synthesis pathways. Furthermore, liver LXR/RXR signaling pathway was altered between LA and TNBC in AA women and may be due to the deficiency of the CYP7B1 enzyme responsible for cholesterol degradation. CONCLUSION: These findings suggest that TNBC in AA women enriched in signaling pathways that are different from TNBC in EA women. Our study draws a link between LXR/RXR expression, cholesterol, obesity, and the TNBC in AA women. |
format | Online Article Text |
id | pubmed-6304259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63042592018-12-26 LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women Torres-Luquis, Odalys Madden, Krystal N’dri, N’sanh MR Berg, Richard Olopade, Olufunmilayo F Ngwa, Wilfred Abuidris, Dafalla Mittal, Suresh Lyn-Cook, Beverly Mohammed, Sulma I Breast Cancer (Dove Med Press) Original Research BACKGROUND: Triple-negative breast cancer (TNBC) is more prevalent in African and African American (AA) women compared to European American (EA) women. African and AA women diagnosed with TNBC experience high frequencies of metastases and less favorable outcomes. Emerging evidence indicates that this disparity may in fact be the result of the uniquely aggressive biology of African and AA disease. PURPOSE: To understand the reasons for TNBC in AA aggressive biology, we designed the present study to examine the proteomic profiles of TNBC and luminal A (LA) breast cancer within and across patients’ racial demographic groups in order to identify proteins or molecular pathways altered in TNBC that offer some explanation for its aggressiveness and potential targets for treatment. MATERIALS AND METHODS: Proteomic profiles of TNBC, LA tumors, and their adjacent normal tissues from AA and EA women were obtained using 2-dimensional gel electrophoresis and bioinformatics, and differentially expressed proteins were validated by Western blot and immunohistochemistry. Our data showed that a number of proteins have significantly altered in expression in LA tumors compared to TNBC, both within and across patients’ racial demographic groups. The differentially overexpressed proteins in TNBC (compared to LA) of AA samples were distinct from those in TNBC (compared to LA) of EA women samples. Among the signaling pathways altered in AA TNBC compared to EA TNBC are innate immune signaling, calpain protease, and pyrimidine de novo synthesis pathways. Furthermore, liver LXR/RXR signaling pathway was altered between LA and TNBC in AA women and may be due to the deficiency of the CYP7B1 enzyme responsible for cholesterol degradation. CONCLUSION: These findings suggest that TNBC in AA women enriched in signaling pathways that are different from TNBC in EA women. Our study draws a link between LXR/RXR expression, cholesterol, obesity, and the TNBC in AA women. Dove Medical Press 2018-12-20 /pmc/articles/PMC6304259/ /pubmed/30588086 http://dx.doi.org/10.2147/BCTT.S185960 Text en © 2019 Torres-Luquis et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Torres-Luquis, Odalys Madden, Krystal N’dri, N’sanh MR Berg, Richard Olopade, Olufunmilayo F Ngwa, Wilfred Abuidris, Dafalla Mittal, Suresh Lyn-Cook, Beverly Mohammed, Sulma I LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women |
title | LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women |
title_full | LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women |
title_fullStr | LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women |
title_full_unstemmed | LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women |
title_short | LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women |
title_sort | lxr/rxr pathway signaling associated with triple-negative breast cancer in african american women |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304259/ https://www.ncbi.nlm.nih.gov/pubmed/30588086 http://dx.doi.org/10.2147/BCTT.S185960 |
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