Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines Journal Article
| Authors: | Lopes, E. C.; Valls, E.; Figueroa, M. E.; Mazur, A.; Meng, F. G.; Chiosis, G.; Laird, P. W.; Schreiber-Agus, N.; Greally, J. M.; Prokhortchouk, E.; Melnick, A. |
| Article Title: | Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines |
| Abstract: | Aberrant CpG methylation of tumor suppressor gene regulatory elements is associated with transcriptional silencing and contributes to malignant transformation of different tissues. It is presumed that methylated DNA sequences recruit repressor machinery to actively shutdown gene expression. The Kaiso protein is a transcriptional repressor expressed in human and murine colorectal tumors that can bind to methylated clusters of CpG dinucleotides. We show here that Kaiso represses methylated tumor suppressor genes and can bind in a methylation-dependent manner to the CDKN2A in human colon cancer cell lines. The contribution of Kaiso to epigenetic silencing was underlined by the fact that Kaiso depletion induced tumor suppressor gene expression without affecting DNA methylation levels. As a consequence, colon cancer cells became susceptible to cell cycle arrest and cell death mediated by chemotherapy. The data suggest that Kaiso is a methylation-dependent "opportunistic" oncogene that silences tumor suppressor genes when they become hypermethylated. Because Kaiso inactivation sensitized colon cancer cell lines to chemotherapy, it is possible that therapeutic targeting of Kaiso could improve the efficacy of current treatment regimens. ©2008 American Association for Cancer Research. |
| Keywords: | controlled study; human cell; cell death; gene targeting; cell cycle; small interfering rna; protein binding; colonic neoplasms; hct116 cells; rna, small interfering; cancer cell culture; cell line, tumor; transfection; dna methylation; transcription factors; oncogene; tumor suppressor gene; chromatin immunoprecipitation; cpg island; colon cancer; cell cycle arrest; dna sequence; gene silencing; cyclin dependent kinase inhibitor 2a; cyclin-dependent kinase inhibitor p16; malignant transformation; dinucleotide; genes, tumor suppressor; repressor gene; regulatory sequence; genes, p16; promoter regions (genetics); kaiso gene |
| Journal Title: | Cancer Research |
| Volume: | 68 |
| Issue: | 18 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-09-15 |
| Start Page: | 7258 |
| End Page: | 7263 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-08-0344 |
| PUBMED: | 18794111 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 21" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus" |
