Breast Cancer: Targets and Therapy (Dec 2018)
LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women
Abstract
Odalys Torres-Luquis,1,2 Krystal Madden,3 N’sanh MR N’dri,1 Richard Berg,4 Olufunmilayo F Olopade,5 Wilfred Ngwa,6,7 Dafalla Abuidris,8 Suresh Mittal,1,2 Beverly Lyn-Cook,9 Sulma I Mohammed1,2 1Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA; 2Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, USA; 3Department of Learning Sciences, University of Illinois at Chicago, Chicago, IL, USA; 4Department of Surgery, Indiana University Health, Lafayette, IN, USA; 5Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA; 6Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA; 7Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; 8Department of Oncology, National Cancer Institute, University of Gezira, Gezira, Sudan; 9Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR, USA 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.Keywords: breast, triple-negative breast cancer, African American, European American, luminal breast cancer, luminal
