RRC ID 62741
Author Kawaguchi K, Kinameri A, Suzuki S, Senga S, Ke Y, Fujii H.
Title The cancer-promoting gene fatty acid-binding protein 5 (FABP5) is epigenetically regulated during human prostate carcinogenesis.
Journal Biochem J
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.
Volume 473(4)
Pages 449-61
Published 2016-2-15
DOI 10.1042/BJ20150926
PII BJ20150926
PMID 26614767
MeSH Cell Line, Tumor DNA Methylation Epigenesis, Genetic* Fatty Acid-Binding Proteins / genetics* Gene Expression Regulation, Neoplastic* Humans Male Middle Aged Promoter Regions, Genetic Prostatic Neoplasms / genetics* Proto-Oncogene Proteins c-myc / metabolism Sp1 Transcription Factor / metabolism
IF 4.097
Human and Animal Cells DU145(RCB2143) LNCap.FGC(RCB2144)