title: The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors.
abstract: A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11REN (KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, L'Aquila 67100, Italy.
authors.forename: M Michela
authors.initials: MM
authors.lastname: Mancarelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Zazzeroni
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccocioppo
authors.forename: Daria
authors.initials: D
authors.lastname: Capece
authors.forename: Agnese
authors.initials: A
authors.lastname: Po
authors.forename: Simona
authors.initials: S
authors.lastname: Murgo
authors.forename: Raffaello
authors.initials: R
authors.lastname: Di Camillo
authors.forename: Christian
authors.initials: C
authors.lastname: Rinaldi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins; D004247:DNA; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology*; D014166:Transferases
chemical_list: D018797:Cell Cycle Proteins; D015221:Potassium Channels; D016329:Sp1 Transcription Factor; D004247:DNA; C488725:KCTD11 protein, human; D014166:Transferases