Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas

Takaya Kobatake, Masaaki Yano, Shinichi Toyooka, Kazunori Tsukuda, Hideaki Dote, Takefumi Kikuchi, Minoru Toyota, Mamoru Oouchida, A. O E Motoi, Hiroshi Date, Harvey I. Pass, Hiroyoshi Doihara, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

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Abstract

The p57KIP2 gene belongs to the Cip/Kip family of CDK inhibitors and has been demonstrated to be a tumor suppressor gene, being inactivated in various types of human cancers. We analyzed the methylation and expression status of p57KIP2 in lung and breast cancers, and in malignant mesotheliomas (MMs). The promoter region of p57KIP2 was determined by methylation-specific PCR (MSP) in samples of lung and breast cancer, and of MM. The expression of the gene in the cell lines was determined by RT-PCR and correlated with the methylation status. Aberrant methylation was detected by MSP in 9 of 27 (33%) and 25 of 78 (32%) lung cancer cell lines and tumors, respectively, 11 of 18 (61%) and 17 of 38 (45%) breast cancer cell lines and tumors, respectively, and 1 of 25 (4%) MM tumors. DNA methylation was detected but rarely in the corresponding non-malignant tissues. In addition, the gene expression was restored in the methylated cell lines following 5-aza-2′-deoxycytidine treatment, confirming that the methylation was indeed responsible for the gene down-regulation. We also examined the relationship between the p57KIP2 methylation status and the clinicopathological features of the primary tumors, and found that there was no relationship between the p57KIP2 methylation status and any of the examined clinicopathological features. In summary, our results demonstrate that p57KIP2 methylation associated with the gene down-regulation is frequently present in lung and breast cancers and plays an important role at the molecular level in the pathogenesis of these cancers.

Original languageEnglish
Pages (from-to)1087-1092
Number of pages6
JournalOncology Reports
Volume12
Issue number5
Publication statusPublished - Nov 2004

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Methylation
Lung Neoplasms
Breast Neoplasms
Genes
decitabine
Tumor Cell Line
Polymerase Chain Reaction
Neoplasms
Down-Regulation
Gene Expression
Malignant Mesothelioma
Cell Line
DNA Methylation
Tumor Suppressor Genes
Genetic Promoter Regions

Keywords

  • Breast cancer
  • Lung cancer
  • Malignant mesothelioma
  • Methylation
  • p57KIP2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kobatake, T., Yano, M., Toyooka, S., Tsukuda, K., Dote, H., Kikuchi, T., ... Shimizu, N. (2004). Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas. Oncology Reports, 12(5), 1087-1092.

Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas. / Kobatake, Takaya; Yano, Masaaki; Toyooka, Shinichi; Tsukuda, Kazunori; Dote, Hideaki; Kikuchi, Takefumi; Toyota, Minoru; Oouchida, Mamoru; Motoi, A. O E; Date, Hiroshi; Pass, Harvey I.; Doihara, Hiroyoshi; Shimizu, Nobuyoshi.

In: Oncology Reports, Vol. 12, No. 5, 11.2004, p. 1087-1092.

Research output: Contribution to journalArticle

Kobatake, T, Yano, M, Toyooka, S, Tsukuda, K, Dote, H, Kikuchi, T, Toyota, M, Oouchida, M, Motoi, AOE, Date, H, Pass, HI, Doihara, H & Shimizu, N 2004, 'Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas', Oncology Reports, vol. 12, no. 5, pp. 1087-1092.
Kobatake T, Yano M, Toyooka S, Tsukuda K, Dote H, Kikuchi T et al. Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas. Oncology Reports. 2004 Nov;12(5):1087-1092.
Kobatake, Takaya ; Yano, Masaaki ; Toyooka, Shinichi ; Tsukuda, Kazunori ; Dote, Hideaki ; Kikuchi, Takefumi ; Toyota, Minoru ; Oouchida, Mamoru ; Motoi, A. O E ; Date, Hiroshi ; Pass, Harvey I. ; Doihara, Hiroyoshi ; Shimizu, Nobuyoshi. / Aberrant methylation of p57KIP2 gene in lung and breast cancers and malignant mesotheliomas. In: Oncology Reports. 2004 ; Vol. 12, No. 5. pp. 1087-1092.
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abstract = "The p57KIP2 gene belongs to the Cip/Kip family of CDK inhibitors and has been demonstrated to be a tumor suppressor gene, being inactivated in various types of human cancers. We analyzed the methylation and expression status of p57KIP2 in lung and breast cancers, and in malignant mesotheliomas (MMs). The promoter region of p57KIP2 was determined by methylation-specific PCR (MSP) in samples of lung and breast cancer, and of MM. The expression of the gene in the cell lines was determined by RT-PCR and correlated with the methylation status. Aberrant methylation was detected by MSP in 9 of 27 (33{\%}) and 25 of 78 (32{\%}) lung cancer cell lines and tumors, respectively, 11 of 18 (61{\%}) and 17 of 38 (45{\%}) breast cancer cell lines and tumors, respectively, and 1 of 25 (4{\%}) MM tumors. DNA methylation was detected but rarely in the corresponding non-malignant tissues. In addition, the gene expression was restored in the methylated cell lines following 5-aza-2′-deoxycytidine treatment, confirming that the methylation was indeed responsible for the gene down-regulation. We also examined the relationship between the p57KIP2 methylation status and the clinicopathological features of the primary tumors, and found that there was no relationship between the p57KIP2 methylation status and any of the examined clinicopathological features. In summary, our results demonstrate that p57KIP2 methylation associated with the gene down-regulation is frequently present in lung and breast cancers and plays an important role at the molecular level in the pathogenesis of these cancers.",
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