Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers

Kunitoshi Tomii, Kazunori Tsukuda, Shinichi Toyooka, Hideaki Dote, Tadashi Hanafusa, Hiroaki Asano, Minoru Naitou, Hiroyoshi Doihara, Takumi Kisimoto, Hideki Katayama, Harvery I. Pass, Hiroshi Date, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p <0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined.

Original languageEnglish
Pages (from-to)566-573
Number of pages8
JournalInternational Journal of Cancer
Volume120
Issue number3
DOIs
Publication statusPublished - Feb 1 2007

Fingerprint

Insulin-Like Growth Factor Binding Protein 3
Methylation
Genes
Neoplasms
Tumor Cell Line
Breast Neoplasms
Stomach Neoplasms
Colorectal Neoplasms
Polymerase Chain Reaction
Tumor Suppressor Genes
DNA Sequence Analysis
Real-Time Polymerase Chain Reaction
Stomach

Keywords

  • Breast cancer
  • Colorectal cancer
  • Gastric cancer
  • IGFBP-3
  • Malignant mesothelioma
  • Methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. / Tomii, Kunitoshi; Tsukuda, Kazunori; Toyooka, Shinichi; Dote, Hideaki; Hanafusa, Tadashi; Asano, Hiroaki; Naitou, Minoru; Doihara, Hiroyoshi; Kisimoto, Takumi; Katayama, Hideki; Pass, Harvery I.; Date, Hiroshi; Shimizu, Nobuyoshi.

In: International Journal of Cancer, Vol. 120, No. 3, 01.02.2007, p. 566-573.

Research output: Contribution to journalArticle

Tomii, Kunitoshi ; Tsukuda, Kazunori ; Toyooka, Shinichi ; Dote, Hideaki ; Hanafusa, Tadashi ; Asano, Hiroaki ; Naitou, Minoru ; Doihara, Hiroyoshi ; Kisimoto, Takumi ; Katayama, Hideki ; Pass, Harvery I. ; Date, Hiroshi ; Shimizu, Nobuyoshi. / Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. In: International Journal of Cancer. 2007 ; Vol. 120, No. 3. pp. 566-573.
@article{d136d013dc364030b621adb503aff584,
title = "Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers",
abstract = "Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46{\%}) and 16 of 24 (67{\%}) GC cell lines and tumors, respectively; 4 of 8 (50{\%}) and 15 of 26 (58{\%}) CRC cell lines and tumors, respectively; 3 of 11 (27{\%}) and 7 of 39 (18{\%}) BC cell lines and tumors, respectively and 1 of 5 (20{\%}) and 18 of 56 (32{\%}) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75{\%}, 12 out of 16 patients) was significantly higher than those from the USA (15{\%}, 6 out of 40 patients) (p <0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined.",
keywords = "Breast cancer, Colorectal cancer, Gastric cancer, IGFBP-3, Malignant mesothelioma, Methylation",
author = "Kunitoshi Tomii and Kazunori Tsukuda and Shinichi Toyooka and Hideaki Dote and Tadashi Hanafusa and Hiroaki Asano and Minoru Naitou and Hiroyoshi Doihara and Takumi Kisimoto and Hideki Katayama and Pass, {Harvery I.} and Hiroshi Date and Nobuyoshi Shimizu",
year = "2007",
month = "2",
day = "1",
doi = "10.1002/ijc.22341",
language = "English",
volume = "120",
pages = "566--573",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers

AU - Tomii, Kunitoshi

AU - Tsukuda, Kazunori

AU - Toyooka, Shinichi

AU - Dote, Hideaki

AU - Hanafusa, Tadashi

AU - Asano, Hiroaki

AU - Naitou, Minoru

AU - Doihara, Hiroyoshi

AU - Kisimoto, Takumi

AU - Katayama, Hideki

AU - Pass, Harvery I.

AU - Date, Hiroshi

AU - Shimizu, Nobuyoshi

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p <0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined.

AB - Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p <0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined.

KW - Breast cancer

KW - Colorectal cancer

KW - Gastric cancer

KW - IGFBP-3

KW - Malignant mesothelioma

KW - Methylation

UR - http://www.scopus.com/inward/record.url?scp=33845696647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845696647&partnerID=8YFLogxK

U2 - 10.1002/ijc.22341

DO - 10.1002/ijc.22341

M3 - Article

C2 - 17096329

AN - SCOPUS:33845696647

VL - 120

SP - 566

EP - 573

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -