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KLF5 enhances SREBP-1 action in androgen-dependent induction of fatty acid synthase in prostate cancer cells

 Min-Young LEE  ;  Jong-Seok MOON  ;  Sahng Wook PARK  ;  Yoo-kyung KOH  ;  Yong-Ho AHN  ;  Kyung-Sup KIM 
 BIOCHEMICAL JOURNAL, Vol.417(1) : 313-322, 2009 
Journal Title
Issue Date
Androgens/pharmacology* ; Blotting, Western ; Cell Line, Tumor ; Fatty Acid Synthases/genetics ; Fatty Acid Synthases/metabolism* ; Gene Expression/drug effects ; Humans ; Immunoprecipitation ; Introns/genetics ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism* ; Male ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Protein Binding/drug effects ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Sterol Regulatory Element Binding Protein 1/genetics ; Sterol Regulatory Element Binding Protein 1/metabolism*
androgen receptor (AR) ; fatty acid synthase (FASN) ; Krüppel-like factor (KLF) family ; sterol-regulatory-element-binding protein-1 (SREBP-1) ; synergism
KLF5 (Krüppel-like factor 5) is a zinc-finger transcription factor that plays a critical role in the regulation of cellular signalling involved in cell proliferation, differentiation and oncogenesis. in the present study, we showed that KLF5 acts as a key regulator controlling the expression of FASN (fatty acid synthase) through an interaction with SREBP-1 (sterol-regulatory-element-binding protein-1) in the androgen-dependent LNCaP prostate cancer cell line. the mRNA level of KLF5 increased when cells were treated with a synthetic androgen, R1881. Furthermore, KLF5 bound to SREBP-1 and enhanced the SREBP-1-mediated increase in FASN promoter activity. the results also demonstrated that the expression of KLF5 in LNCaP prostate cancer cells enhanced FASN expression, whereas silencing of KLF5 by small interfering RNA down-regulated FASN expression. the proximal promoter region and the first intron of the FASN gene contain multiple CACCC elements that mediate the transcriptional regulation of the gene by KLF5. However, other lipogenic and cholesterogenic genes, such as those encoding acetyl-CoA carboxylase, ATP-citrate lyase, the LDL (low-density lipoprotein) receptor, HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) synthase and HMG-CoA reductase are irresponsive to KLF5 expression, owing to the absence of CACCC elements in their promoter regions. Taken together, these results suggest that the FASN gene is activated by the synergistic action of KLF5 and SREBP-1, which was induced by androgen in androgen-dependent prostate cancer cells.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Moon, Jong-Seok(문종석)
Park, Sahng Wook(박상욱) ORCID logo https://orcid.org/0000-0002-9594-7074
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Lee, Min Young(이민영)
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