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A fatty acid‐binding protein 7/RXRβ pathway enhances survival and proliferation in triple‐negative breast cancer
Author(s) -
Liu RongZong,
Graham Kathryn,
Glubrecht Darryl D,
Lai Raymond,
Mackey John R,
Godbout Roseline
Publication year - 2012
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4001
Subject(s) - triple negative breast cancer , breast cancer , cancer research , cancer , chemistry , medicine , biology , oncology
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. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.