mRNA expression of genes altered by 5-azacytidine treatment in cancer cell lines is associated with clinicopathological parameters of human cancers

Yae Kanai, S. Ushijima, Yoshimasa Saito, Y. Nakanishi, Michiie Sakamoto, S. Hirohashi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: We attempted to identify tumor-related genes whose expression is affected by DNA methylation and that participate in the determination of the biological characteristics of human cancers. Methods and materials: We used the differential display method in ten 5-azacytidine-treated human cancer cell lines. Timedependent induction of mRNA expression of Wip1, TROP2, B4-2 protein, BRCA-2 region transcription unit CG005, cofilin, ROCK, CD44, and interferon-inducible protein 6-16 was observed during 5-azacytidine treatment. We then evaluated the mRNA expression of these genes in 26 stomach and 32 colorectal cancers and 44 hepatocellular carcinomas (HCCs) and in the corresponding non-cancerous tissues. Results: Significantly reduced mRNA expression of Wip1, B4-2, and cofilin in stomach cancers, of Wip1, B4-2, BRCA-2 region transcription unit CG005, cofilin, and ROCK in colorectal cancers, and of TROP2, B4-2, and BRCA-2 region transcription unit CG005 in HCCs, was observed in comparison with the corresponding non-cancerous tissues, whereas overexpression of TROP2 was detected in colorectal cancers. Reduced expression of Wip1 and BRCA-2 region transcription unit CG005 was significantly correlated with poorer differentiation of HCCs, and mRNA expression of these genes was significantly reduced in HCCs associated with portal vein involvement compared with HCCs without such involvement. Expression of TROP2 mRNA was significantly higher in chronically diseased liver from HCC patients compared with histologically normal liver, but was reduced in progressed HCCs. Reduced expression of B4-2 protein was observed in association with hepatitis B virus infection of HCC patients. Conclusions: These data suggest that DNA methylation may play a role in human multistage carcinogenesis through direct or indirect regulation of multiple tumor-related genes.

Original languageEnglish
Pages (from-to)697-706
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume127
Issue number12
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Azacitidine
Hepatocellular Carcinoma
Gene Expression
Cell Line
Messenger RNA
Neoplasms
Actin Depolymerizing Factors
Colorectal Neoplasms
DNA Methylation
Cofilin 2
Proteins
Virus Diseases
Portal Vein
Hepatitis B virus
Interferons
Stomach Neoplasms
Liver Diseases
Stomach
Carcinogenesis
Liver

Keywords

  • 5-azacytidine
  • B4-2 protein
  • Cofilin
  • NA methylation
  • TROP2
  • Wip1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{b0451220b1ed46e786a43b564216e0fa,
title = "mRNA expression of genes altered by 5-azacytidine treatment in cancer cell lines is associated with clinicopathological parameters of human cancers",
abstract = "Objective: We attempted to identify tumor-related genes whose expression is affected by DNA methylation and that participate in the determination of the biological characteristics of human cancers. Methods and materials: We used the differential display method in ten 5-azacytidine-treated human cancer cell lines. Timedependent induction of mRNA expression of Wip1, TROP2, B4-2 protein, BRCA-2 region transcription unit CG005, cofilin, ROCK, CD44, and interferon-inducible protein 6-16 was observed during 5-azacytidine treatment. We then evaluated the mRNA expression of these genes in 26 stomach and 32 colorectal cancers and 44 hepatocellular carcinomas (HCCs) and in the corresponding non-cancerous tissues. Results: Significantly reduced mRNA expression of Wip1, B4-2, and cofilin in stomach cancers, of Wip1, B4-2, BRCA-2 region transcription unit CG005, cofilin, and ROCK in colorectal cancers, and of TROP2, B4-2, and BRCA-2 region transcription unit CG005 in HCCs, was observed in comparison with the corresponding non-cancerous tissues, whereas overexpression of TROP2 was detected in colorectal cancers. Reduced expression of Wip1 and BRCA-2 region transcription unit CG005 was significantly correlated with poorer differentiation of HCCs, and mRNA expression of these genes was significantly reduced in HCCs associated with portal vein involvement compared with HCCs without such involvement. Expression of TROP2 mRNA was significantly higher in chronically diseased liver from HCC patients compared with histologically normal liver, but was reduced in progressed HCCs. Reduced expression of B4-2 protein was observed in association with hepatitis B virus infection of HCC patients. Conclusions: These data suggest that DNA methylation may play a role in human multistage carcinogenesis through direct or indirect regulation of multiple tumor-related genes.",
keywords = "5-azacytidine, B4-2 protein, Cofilin, NA methylation, TROP2, Wip1",
author = "Yae Kanai and S. Ushijima and Yoshimasa Saito and Y. Nakanishi and Michiie Sakamoto and S. Hirohashi",
year = "2001",
language = "English",
volume = "127",
pages = "697--706",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "12",

}

TY - JOUR

T1 - mRNA expression of genes altered by 5-azacytidine treatment in cancer cell lines is associated with clinicopathological parameters of human cancers

AU - Kanai, Yae

AU - Ushijima, S.

AU - Saito, Yoshimasa

AU - Nakanishi, Y.

AU - Sakamoto, Michiie

AU - Hirohashi, S.

PY - 2001

Y1 - 2001

N2 - Objective: We attempted to identify tumor-related genes whose expression is affected by DNA methylation and that participate in the determination of the biological characteristics of human cancers. Methods and materials: We used the differential display method in ten 5-azacytidine-treated human cancer cell lines. Timedependent induction of mRNA expression of Wip1, TROP2, B4-2 protein, BRCA-2 region transcription unit CG005, cofilin, ROCK, CD44, and interferon-inducible protein 6-16 was observed during 5-azacytidine treatment. We then evaluated the mRNA expression of these genes in 26 stomach and 32 colorectal cancers and 44 hepatocellular carcinomas (HCCs) and in the corresponding non-cancerous tissues. Results: Significantly reduced mRNA expression of Wip1, B4-2, and cofilin in stomach cancers, of Wip1, B4-2, BRCA-2 region transcription unit CG005, cofilin, and ROCK in colorectal cancers, and of TROP2, B4-2, and BRCA-2 region transcription unit CG005 in HCCs, was observed in comparison with the corresponding non-cancerous tissues, whereas overexpression of TROP2 was detected in colorectal cancers. Reduced expression of Wip1 and BRCA-2 region transcription unit CG005 was significantly correlated with poorer differentiation of HCCs, and mRNA expression of these genes was significantly reduced in HCCs associated with portal vein involvement compared with HCCs without such involvement. Expression of TROP2 mRNA was significantly higher in chronically diseased liver from HCC patients compared with histologically normal liver, but was reduced in progressed HCCs. Reduced expression of B4-2 protein was observed in association with hepatitis B virus infection of HCC patients. Conclusions: These data suggest that DNA methylation may play a role in human multistage carcinogenesis through direct or indirect regulation of multiple tumor-related genes.

AB - Objective: We attempted to identify tumor-related genes whose expression is affected by DNA methylation and that participate in the determination of the biological characteristics of human cancers. Methods and materials: We used the differential display method in ten 5-azacytidine-treated human cancer cell lines. Timedependent induction of mRNA expression of Wip1, TROP2, B4-2 protein, BRCA-2 region transcription unit CG005, cofilin, ROCK, CD44, and interferon-inducible protein 6-16 was observed during 5-azacytidine treatment. We then evaluated the mRNA expression of these genes in 26 stomach and 32 colorectal cancers and 44 hepatocellular carcinomas (HCCs) and in the corresponding non-cancerous tissues. Results: Significantly reduced mRNA expression of Wip1, B4-2, and cofilin in stomach cancers, of Wip1, B4-2, BRCA-2 region transcription unit CG005, cofilin, and ROCK in colorectal cancers, and of TROP2, B4-2, and BRCA-2 region transcription unit CG005 in HCCs, was observed in comparison with the corresponding non-cancerous tissues, whereas overexpression of TROP2 was detected in colorectal cancers. Reduced expression of Wip1 and BRCA-2 region transcription unit CG005 was significantly correlated with poorer differentiation of HCCs, and mRNA expression of these genes was significantly reduced in HCCs associated with portal vein involvement compared with HCCs without such involvement. Expression of TROP2 mRNA was significantly higher in chronically diseased liver from HCC patients compared with histologically normal liver, but was reduced in progressed HCCs. Reduced expression of B4-2 protein was observed in association with hepatitis B virus infection of HCC patients. Conclusions: These data suggest that DNA methylation may play a role in human multistage carcinogenesis through direct or indirect regulation of multiple tumor-related genes.

KW - 5-azacytidine

KW - B4-2 protein

KW - Cofilin

KW - NA methylation

KW - TROP2

KW - Wip1

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M3 - Article

VL - 127

SP - 697

EP - 706

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 12

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