title: Regulation of the FABP7 gene by PAX6 in malignant glioma cells.
abstract: Brain fatty acid-binding protein (FABP7) and PAX6 are both expressed in radial glial cells and have been implicated in neurogenesis and glial cell differentiation. FABP7 and PAX6 have also been postulated to play a role in malignant glioma cell growth and invasion. Here, we address the role of PAX6 in regulating FABP7 gene expression in malignant glioma cells. We report that PAX6 and FABP7 RNA are generally co-expressed in malignant glioma cell lines, tumors and tumor neurospheres. Using the CAT reporter gene assay, we show that FABP7 promoter activity is upregulated by PAX6. Sequential deletion analysis of the FABP7 promoter, combined with gel shift and supershift assays demonstrate the presence of a PAX6 responsive region located upstream of the FABP7 gene, at -862 to -1033 bp. Inclusion of sequences between -1.2 and -1.8 kb reduced CAT activity, suggesting the presence of a repressor element within this region. While PAX6 overexpression did not induce endogenous FABP7 expression in FABP7-negative cells, knock-down of PAX6 in PAX6-positive malignant glioma cells resulted in reduced FABP7 levels. These data provide the first evidence of direct transactivation of the FABP7 proximal promoter by PAX6 and suggest a synergistic mechanism for PAX6 and other co-factor(s) in regulating FABP7 expression in malignant glioma.
authors.affiliation: Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
authors.forename: Rong-Zong
authors.initials: RZ
authors.lastname: Liu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Monckton
authors.forename: Roseline
authors.initials: R
authors.lastname: Godbout
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins