Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype
| Autor: | Claudia Lüke, Ruth Knüchel, Manfred Dietel, Ladhoff Am, Glen Kristiansen, Michael Rose, Holger Moch, Florian R. Fritzsche, Josefine Gerhardt, Thomas A. Gorr, Edgar Dahl, Cordelia Geisler, Jean-Philippe Theurillat, Zsuzsanna Varga |
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| Přispěvatelé: | University of Zurich, Kristiansen, G |
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
medicine.medical_specialty Neoplasms Hormone-Dependent Estrogen receptor 610 Medicine & health Breast Neoplasms Biology fatty acids Cohort Studies breast cancer Breast cancer 10049 Institute of Pathology and Molecular Pathology Cell Line Tumor Internal medicine medicine Humans 1306 Cancer Research Neoplasm Invasiveness RNA Messenger Receptor Molecular Diagnostics Myoglobin Cancer Middle Aged 10081 Institute of Veterinary Physiology Prognosis luminal type medicine.disease Immunohistochemistry oestrogen receptor Fatty acid synthase Carcinoma Intraductal Noninfiltrating Phenotype Endocrinology Real-time polymerase chain reaction Oncology biology.protein Cancer research 570 Life sciences biology 2730 Oncology Female Breast disease |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. Methods: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-α (ERα)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1α (HIF-1α), HIF-2α, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERα or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. Results: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2α and CAIX, but not to HIF-1α or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERα or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. Conclusion: We conclude that in breast cancer, Mb is co-expressed with ERα and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours. |
| Databáze: | OpenAIRE |
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