title: CRABP-II- and FABP5-independent responsiveness of human glioblastoma cells to all-trans retinoic acid.
abstract: Glioblastomas respond differently to all-trans retinoic acid (RA) for unknown reasons. Because CRABP-II and FABP5 mediate RA intracellular signaling respectively and lead to distinct biological consequences, their expression patterns in different grades of astrocytomas and the glioblastoma cells lines LN18, LN428 and U251 were examined to identify potential correlations with RA sensitivities. The response of glioblastoma cells to RA, decitabine or the FABP5 competitive inhibitor, BMS309403, was analyzed. CRABP-II and FABP5 were expressed to varying degrees by the 84-astrocytoma cases examined. Treatment of LN428, U251 and LN18 cells with RA failed to suppress their growth; however, U251 proliferation was inhibited by decitabine. The combination of decitabine and RA suppressed the growth of all three cell lines and induced significant apoptosis of LN428 and U251 cells. Both CRABP-II and FABP5 were transcribed in the three cell lines but FABP5 proteins were undetectable in U251 cells. The ratio of CRABP-II to FABP5 was not altered after RA, decitabine or RA and decitabine treatment and the resistance of cells to RA was not reversed by BMS309403 treatment. In conclusion, CRABP-II and FABP5 expression patterns are neither related to the tumor grades nor correlated with RA sensitivity. Additional molecular factors may be present that determines the sensitivity of glioblastoma cells to RA. Dicitabine may improve the sensitivity of glioblastoma cells to RA, however, its underlying mechanism and its in vivo feasibility need to be investigated.
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Shi-Lin
authors: SL
authors: Xia
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Mo-Li
authors: ML
authors: Wu
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Hong
authors: H
authors: Li
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Jia-Hui
authors: JH
authors: Wang
authors: Department of Hematology, PLA 210 Hospital, Dalian, China.
authors: Nan-Nan
authors: NN
authors: Chen
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Xiao-Yan
authors: XY
authors: Chen
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Qing-You
authors: QY
authors: Kong
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Zheng
authors: Z
authors: Sun
authors: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
authors: Jia
authors: J
authors: Liu
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D046888:Tissue Array Analysis; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin
keywords: CRABP-II; FABP5; all-trans retinoic acid; chemosensitivity; glioblastoma