Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer
Open Access
- 16 December 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 10 (1), 686
- https://doi.org/10.1186/1471-2407-10-686
Abstract
Background Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women. Methods A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry. Results Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer. Conclusion Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy.Keywords
This publication has 28 references indexed in Scilit:
- First Epidemiological Analysis of Breast Cancer Incidence and Tumor Characteristics after Implementation of Population-Based Digital Mammography ScreeningRöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2009
- Diagnostic importance of overexpression of Bmi-1 mRNA in early breast cancersInternational Journal of Oncology, 2009
- Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissueBreast Cancer Research and Treatment, 2009
- Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patientsBreast Cancer Research, 2007
- Mel-18 Acts as a Tumor Suppressor by Repressing Bmi-1 Expression and Down-regulating Akt Activity in Breast Cancer CellsCancer Research, 2007
- Mel-18, a Polycomb Group Protein, Regulates Cell Proliferation and Senescence via Transcriptional Repression of Bmi-1 and c-Myc OncoproteinsMolecular Biology of the Cell, 2007
- Evaluation and validation of candidate endogenous control genes for real-time quantitative PCR studies of breast cancerBMC Molecular Biology, 2007
- Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem CellsCancer Research, 2006
- Bmi-1 Is a Novel Molecular Marker of Nasopharyngeal Carcinoma Progression and Immortalizes Primary Human Nasopharyngeal Epithelial CellsCancer Research, 2006
- Unique Polycomb Gene Expression Pattern in Hodgkin's Lymphoma and Hodgkin's Lymphoma-Derived Cell LinesThe American Journal of Pathology, 2004