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 language | English |
|---|---|
| Pages (from-to) | 566-573 |
| Number of pages | 8 |
| Journal | International Journal of Cancer |
| Volume | 120 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 1 2007 |
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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 journal › Article
}
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 -