title: Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy.
abstract: 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 clinicopathological 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.
authors.affiliation: Department of Oncology, Cross Cancer Institute, School of Cancer, Engineering and Imaging Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rong-Zong
authors.initials: RZ
authors.lastname: Liu
authors.forename: Kathryn
authors.initials: K
authors.lastname: Graham
authors.forename: Darryl D
authors.initials: DD
authors.lastname: Glubrecht
authors.forename: Devon R
authors.initials: DR
authors.lastname: Germain
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
authors.forename: Roseline
authors.initials: R
authors.lastname: Godbout
mesh_terms: D000368:Aged; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin