A fatty acid-binding protein 7/RXRβ pathway enhances survival and proliferation in triple-negative breast cancer.
FABP7 has been implicated in tumour cell proliferation, cell migration, and poor prognosis in patients with high-grade astrocytoma and melanoma. In this study, we examine FABP7 expression in a cohort of 176 primary breast cancers by gene profiling and tissue microarray immunostaining. We show that FABP7 is significantly up-regulated in triple-negative breast cancer. Elevated FABP7 levels are associated with poor prognosis, absence of oestrogen and progesterone hormone receptors (ER, PR) and HER2, increased cell proliferation, and high tumour grade. Depletion of FABP7 in the ER/PR-negative cell line, MDA-MB-435S, significantly reduced cell growth rate and sensitized the cells to growth inhibition by omega-3 docosahexaenoic acid (DHA). A target of DHA-bound FABP7 in the nucleus is RXRβ, a retinoid-activated nuclear receptor that functions as a transcription factor by either homodimerizing or heterodimerizing with other nuclear receptors such as PPARs. Based on our microarray data, RXRβ, like FABP7, is an adverse prognostic factor for breast cancer. We propose that the DHA-FABP7-RXRβ pathway promotes cell survival/proliferation in triple-negative breast cancer. Targeting this pathway may thus provide an alternate route for the treatment of triple-negative breast cancer.
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada, T6G 1Z2.
Rong-Zong
RZ
Liu
Kathryn
K
Graham
Darryl D
DD
Glubrecht
Raymond
R
Lai
John R
JR
Mackey
Roseline
R
Godbout
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002352:Carrier Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D000071438:Fatty Acid-Binding Protein 7; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D012333:RNA, Messenger / Q000378:metabolism; D049230:Retinoid X Receptor beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D012333:RNA, Messenger; D049230:Retinoid X Receptor beta; D025521:Tumor Suppressor Proteins; D004281:Docosahexaenoic Acids