A fatty acid-binding protein 7/RXRbeta pathway enhances survival and proliferation in triple-negative breast cancer
The Journal of Pathology,
L R-Z et al. – The DHA-FABP7-RXRbeta 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.Methods
- We examined 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 RXRbeta, 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, RXRbeta, like FABP7, is an adverse prognostic factor for breast cancer.