The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors.
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.
Mancarelli
M Michela
MM
Department of Experimental Medicine, University of L'Aquila, L'Aquila 67100, Italy.
Zazzeroni
Francesca
F
Ciccocioppo
Lucia
L
Capece
Daria
D
Po
Agnese
A
Murgo
Simona
S
Di Camillo
Raffaello
R
Rinaldi
Christian
C
Ferretti
Elisabetta
E
Gulino
Alberto
A
Alesse
Edoardo
E
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
D018797:Cell Cycle Proteins; D015221:Potassium Channels; D016329:Sp1 Transcription Factor; D004247:DNA; C488725:KCTD11 protein, human; D014166:Transferases