title: The cancer-promoting gene fatty acid-binding protein 5 (FABP5) is epigenetically regulated during human prostate carcinogenesis.
abstract: FABPs (fatty-acid-binding proteins) are a family of low-molecular-mass intracellular lipid-binding proteins consisting of ten isoforms. FABPs are involved in binding and storing hydrophobic ligands such as long-chain fatty acids, as well as transporting these ligands to the appropriate compartments in the cell. FABP5 is overexpressed in multiple types of tumours. Furthermore, up-regulation of FABP5 is strongly associated with poor survival in triple-negative breast cancer. However, the mechanisms underlying the specific up-regulation of the FABP5 gene in these cancers remain poorly characterized. In the present study, we determined that FABP5 has a typical CpG island around its promoter region. The DNA methylation status of the CpG island in the FABP5 promoter of benign prostate cells (PNT2), prostate cancer cells (PC-3, DU-145, 22Rv1 and LNCaP) and human normal or tumour tissue was assessed by bisulfite sequencing analysis, and then confirmed by COBRA (combined bisulfite restriction analysis) and qAMP (quantitative analysis of DNA methylation using real-time PCR). These results demonstrated that overexpression of FABP5 in prostate cancer cells can be attributed to hypomethylation of the CpG island in its promoter region, along with up-regulation of the direct trans-acting factors Sp1 (specificity protein 1) and c-Myc. Together, these mechanisms result in the transcriptional activation of FABP5 expression during human prostate carcinogenesis. Importantly, silencing of Sp1, c-Myc or FABP5 expression led to a significant decrease in cell proliferation, indicating that up-regulation of FABP5 expression by Sp1 and c-Myc is critical for the proliferation of prostate cancer cells.
authors.affiliation: Interdisciplinary Graduate School of Science and Technology, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kinameri
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Senga
authors.affiliation: Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, 5/6th Floor, Duncan Building, University of Liverpool, Daulby Street, Liverpool L69 3GA, U.K.
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Interdisciplinary Graduate School of Science and Technology, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan hfujii@shinshu-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D016329:Sp1 Transcription Factor
keywords: DNA methylation; FABP5; epigenetics; fatty-acid-binding proteins (FABPs); metastasis; prostate cancer