Zehra Kaya1,2, Mustafa Akkiprik1, Sevgi Karabulut1,3, Irem Peker1, Gokce Gullu Amuran1, Tolga Ozmen4, Bahadır M Gulluoglu4, Handan Kaya5, Ayse Ozer1. 1. Medical Biology Department, School of Medicine, Marmara University, Istanbul, Turkey. 2. Medical Biology Department, School of Medicine, Yüzüncü Yıl University, Van, Turkey. 3. Health Services Vocational School, Bayburt University, Bayburt, Turkey. 4. General Surgery, School of Medicine, Marmara University, Istanbul, Turkey. 5. Pathology Department, School of Medicine, Marmara University, Istanbul, Turkey.
Abstract
BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. RESULTS: Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. CONCLUSION: These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.
BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of humanbreast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. RESULTS: Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. CONCLUSION: These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.
Authors: Y Amemiya; W Yang; T Benatar; S Nofech-Mozes; A Yee; H Kahn; C Holloway; Arun Seth Journal: Breast Cancer Res Treat Date: 2010-05-13 Impact factor: 4.872
Authors: Paul Smith; Linda J Nicholson; Nelofer Syed; Annette Payne; Louise Hiller; Ornella Garrone; Marcella Occelli; Milena Gasco; Tim Crook Journal: Clin Cancer Res Date: 2007-07-15 Impact factor: 12.531