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Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors.
Oncogene. 2002 Apr 18; 21(17):2741-9.O

Abstract

To clarify the role of DNA methylation in the silencing of the expression of cyclin-dependent kinase inhibitor p57KIP2 seen in certain tumors, we investigated the methylation status of its 5' CpG island in various tumor cell lines and primary cancers. Dense methylation of the region around the transcription start site was detected in 1 out of 10 colorectal, 2 out of 8 gastric, and 6 out of 14 hematopoietic tumor cell lines and in 5 out of 35 (14%) gastric, 6 out of 20 (30%) hepatocellular, and 2 out of 18 (11%) pancreatic cancers; 7 out of 25 (28%) acute myeloid leukemia cases also showed methylation of the p57KIP2 gene, which strongly correlated with the CpG island methylator phenotype (P<0.001). Detailed mapping revealed that dense methylation of the region around the transcription start site (-300 to +400), but not of the edges of the CpG island, was closely associated with gene silencing. 5-aza-2'-deoxycytidine, a methyltransferase inhibitor, restored expression of p57KIP2, and chromatin immunoprecipitation using anti-histone H3 and H4 antibodies showed histone to be deacetylated in cell lines where p57KIP2 was methylated at the transcription start site. Regional methylation and histone deacetylation thus appear to be crucially involved in the silencing of p57KIP2 expression in human tumors.

Authors+Show Affiliations

First Department of Internal Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11965547

Citation

Kikuchi, Takefumi, et al. "Inactivation of p57KIP2 By Regional Promoter Hypermethylation and Histone Deacetylation in Human Tumors." Oncogene, vol. 21, no. 17, 2002, pp. 2741-9.
Kikuchi T, Toyota M, Itoh F, et al. Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. Oncogene. 2002;21(17):2741-9.
Kikuchi, T., Toyota, M., Itoh, F., Suzuki, H., Obata, T., Yamamoto, H., Kakiuchi, H., Kusano, M., Issa, J. P., Tokino, T., & Imai, K. (2002). Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. Oncogene, 21(17), 2741-9.
Kikuchi T, et al. Inactivation of p57KIP2 By Regional Promoter Hypermethylation and Histone Deacetylation in Human Tumors. Oncogene. 2002 Apr 18;21(17):2741-9. PubMed PMID: 11965547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. AU - Kikuchi,Takefumi, AU - Toyota,Minoru, AU - Itoh,Fumio, AU - Suzuki,Hiromu, AU - Obata,Toshiro, AU - Yamamoto,Hiroyuki, AU - Kakiuchi,Hideki, AU - Kusano,Masanobu, AU - Issa,Jean-Pierre J, AU - Tokino,Takashi, AU - Imai,Kohzoh, PY - 2001/10/15/received PY - 2002/01/29/revised PY - 2002/01/31/accepted PY - 2002/4/20/pubmed PY - 2002/5/15/medline PY - 2002/4/20/entrez SP - 2741 EP - 9 JF - Oncogene JO - Oncogene VL - 21 IS - 17 N2 - To clarify the role of DNA methylation in the silencing of the expression of cyclin-dependent kinase inhibitor p57KIP2 seen in certain tumors, we investigated the methylation status of its 5' CpG island in various tumor cell lines and primary cancers. Dense methylation of the region around the transcription start site was detected in 1 out of 10 colorectal, 2 out of 8 gastric, and 6 out of 14 hematopoietic tumor cell lines and in 5 out of 35 (14%) gastric, 6 out of 20 (30%) hepatocellular, and 2 out of 18 (11%) pancreatic cancers; 7 out of 25 (28%) acute myeloid leukemia cases also showed methylation of the p57KIP2 gene, which strongly correlated with the CpG island methylator phenotype (P<0.001). Detailed mapping revealed that dense methylation of the region around the transcription start site (-300 to +400), but not of the edges of the CpG island, was closely associated with gene silencing. 5-aza-2'-deoxycytidine, a methyltransferase inhibitor, restored expression of p57KIP2, and chromatin immunoprecipitation using anti-histone H3 and H4 antibodies showed histone to be deacetylated in cell lines where p57KIP2 was methylated at the transcription start site. Regional methylation and histone deacetylation thus appear to be crucially involved in the silencing of p57KIP2 expression in human tumors. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11965547/Inactivation_of_p57KIP2_by_regional_promoter_hypermethylation_and_histone_deacetylation_in_human_tumors_ L2 - https://doi.org/10.1038/sj.onc.1205376 DB - PRIME DP - Unbound Medicine ER -