title: Clusterin is epigenetically regulated in prostate cancer.
abstract: Lack of good models has complicated investigations on the mechanisms of prostate cancer. By far, the most commonly used transgenic mouse model of prostate cancer is TRAMP, which, however, has not been fully characterized for genetic and epigenetic aberrations. Here, we screened TRAMP-derived C2 cell line for the alterations using different microarray approaches, and compared it to human prostate cancer. TRAMP-C2 had relatively few genomic copy number alterations according to array comparative genomic hybridization (aCGH). However, the gene copy number and expression were significantly correlated (p < 0.001). Screening genes for promoter hypermethylation using demethylation treatment with 5-aza-2'-deoxycytidine and subsequent expression profiling indicated 43 putatively epigenetically silenced genes. Further studies revealed that clusterin is methylated in the TRAMP-C2 cell line, as well as in the human prostate cancer cell line LNCaP. Its expression was found to be significantly reduced (p < 0.01) in untreated and hormone-refractory human prostate carcinomas. Together with known function of clusterin, the data suggest an epigenetic component in the regulation of clusterin in prostate cancer.
authors.affiliation: Institute of Medical Technology, University of Tampere, and Tampere University Hospital, Tampere, Finland.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Rauhala
authors.forename: Kati P
authors.initials: KP
authors.lastname: Porkka
authors.forename: Outi R
authors.initials: OR
authors.lastname: Saramäki
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D051152:Clusterin / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C495242:CLU protein, human; D051152:Clusterin