title: Downregulation of the tumor suppressor HSPB7, involved in the p53 pathway, in renal cell carcinoma by hypermethylation.
abstract: In order to identify genes involved in renal carcinogenesis, we analyzed the expression profile of renal cell carcinomas (RCCs) using microarrays consisting of 27,648 cDNA or ESTs, and found a small heat shock protein, HSPB7, to be significantly and commonly downregulated in RCC. Subsequent quantitative PCR (qPCR) and immunohistochemical (IHC) analyses confirmed the downregulation of HSPB7 in RCC tissues and cancer cell lines in both transcriptional and protein levels. Bisulfite sequencing of a genomic region of HSPB7 detected DNA hypermethylation of some segments of HSPB7 in RCC cells and concordantly 5-aza-2'-deoxycytidine (5-Aza-dC) treatment of cancer cells restored HSPB7 expression significantly. Ectopic introduction of HSPB7 in five RCC cell lines remarkably suppressed cancer cell growth. Interestingly, we found that HSPB7 expression could be induced by p53 in a dose-dependent manner, indicating that this gene functions in the p53 pathway. Our results imply that HSBP7 is likely to be a tumor suppressor gene regulated by p53 and its downregulation by hypermethylation may play a critical role in renal carcinogenesis.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Lin
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Tanikawa
authors.affiliation: Department of Urology, School of Medicine, Kochi University, Kochi 783-8505, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D055551:HSP27 Heat-Shock Proteins; C550985:HSPB7 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077209:Decitabine; D001374:Azacitidine