Recent studies using animal models suggest that expression of FABP5 drives the stimulation of cell growth observed in estrogen receptor (ER)-negative breast cancer cells on exposure to retinoic acid (RA). The purpose of this study was to investigate the clinico-pathological significance of FABP5 in breast cancer and to evaluate FABP5 as a prognostic marker and a possible novel therapeutic target in breast cancer. Gene expression microarray analysis revealed a significant correlation between elevated FABP5 RNA levels and ER/progesterone receptor (PR)-negative status, high tumor grade, and poor prognosis. Tissue microarray analysis demonstrated similar correlations with cytoplasmic FABP5 protein. Based on multivariate proportional regression analysis, cytoplasmic FABP5 is a significant and independent prognostic marker of overall survival and recurrence-free survival in breast cancer. The effects of FABP5 on tumor growth appear to be mediated primarily through cytoplasmic FABP, because no correlation was found between nuclear FABP5 and ER/PR-negative status, recurrence, and survival. FABP5 knockdown in breast cancer cell lines demonstrates a correlation between FABP5 levels and growth response to RA. We propose a model whereby growth-promoting FABP5 competes with growth-inhibiting CRABP2 for RA, with retention of RA in the cytoplasm by FABP5 preventing the inhibition of tumor growth.
Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy
Riferimento:
Am J Pathol. 2011 Mar;178(3):997-1008
Autori:
Liu RZ, Graham K, Glubrecht DD, Germain DR, Mackey JR, Godbout R.
Fonte:
Am J Pathol. 2011 Mar;178(3):997-1008
Anno:
2011
Azione:
Nelle linee cellulari del cancro alla mammella vi è correlazione tra i livelli del gene FABP5 e l'influenza sulla crescita indotta da acido retinoico (RA).
Target:
RA/cancro della mammella.
Sostanze: