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Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lopes, Eloisi Caldas Valls, Ester Figueroa, Maria Eugenia Prado Mazur, Alexander Meng, Fan-guo Chiosis, Gabriela Laird, Peter W. Schreiber-Agus, Nicole Greally, John M. Prokhortchouk, Egor B. Melnick, Ari |
| Copyright Year | 2008 |
| 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. |
| Starting Page | 116 |
| Ending Page | 127 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/68/18/7258.full.pdf |
| PubMed reference number | 18794111v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-08-0344 |
| DOI | 10.1158/0008-5472.can-08-0344 |
| Journal | Cancer research |
| Volume Number | 68 |
| Issue Number | 18 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Body tissue Cell Cycle Arrest Cell Death Colon Carcinoma Colonic Neoplasms Colorectal Neoplasms Current Therapy Cyclin-Dependent Kinase Inhibitor 2A, human Epigenetic Silencing Gene Expression Genes, Suppressor Methylation Oncogenes Transcription Repressor/Corepressor Transcription, Genetic Tumor Suppressor Genes ZBTB33 gene cancer cell cellular targeting |
| Content Type | Text |
| Resource Type | Article |
