Expressions of individual PHDs associate with good prognostic factors and increased proliferation in breast cancer patients

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• 作者：Emmi Peurala (12)
  Peppi Koivunen (3)
  Risto Bloigu (4)
  Kirsi-Maria Haapasaari (1)
  Arja Jukkola-Vuorinen (25) arja.jukkola-vuorinen@ppshp.fi
• 关键词：HIF – ; Prolyl 4 ; hydroxylases – ; PHD – ; Breast cancer – ; Apoptosis
• 刊名：Breast Cancer Research and Treatment
• 出版年：2012
• 出版时间：May 2012
• 年：2012
• 卷：133
• 期：1
• 页码：179-188
• 全文大小：697.9 KB
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• 作者单位：1. Department of Pathology, University of Oulu, Aapistie 5b, P.O. Box 5000, 90014 Oulu, Finland2. Department of Oncology and Radiotherapy, University of Oulu, Kajaanintie 50, P.O. Box 5000, 90014 Oulu, Finland3. Department of Medical Biochemistry and Molecular Biology and Oulu Center for Cell鈥揗atrix Research, University of Oulu, Aapistie 7, P.O. Box 5000, 90014 Oulu, Finland4. Medical Informatics and Statistics Research Group, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland5. Department of Oncology and Radiotherapy, University of Oulu, Oulu University Hospital, P.O. Box 22, 90029 Oulu, Finland
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

Tumor hypoxia-inducible transcription factor (HIF) overexpression often associates with a poor prognosis. Stability of the HIF-α subunits is regulated by HIF prolyl 4-hydroxylases, PHD1–3. We assessed here immunohistochemical expression of PHD1–3 and HIF-1α and 2α in patients with invasive ductal breast carcinoma (n = 102) and correlated their expression levels with main clinical prognostic factors and survival. PHD1 expression correlated with high proliferation, and these tumors were mainly estrogen receptor-negative. PHD3 expression declined in tumors of large size, poor differentiation, and high proliferation. There was a tendency for increased breast cancer-specific survival and longer disease-free survival among patients with high tumor PHD2 expression. Surprisingly, PHD1–3 expression did not correlate with HIF-1α or HIF-2α downregulation. However, HIF-2α expression correlated independently with low tumor stage and HIF-1α expression had a tendency for decreased breast cancer-specific survival. PHD1 and 3 appear to be HIF-independent factors in breast cancer. Not all PHD1 associated proliferation is estrogen-dependent and it is associated with a poor prognosis of cancer. PHD3 may be an important regulator of apoptosis and it is mainly found in tumors with good prognosis. PHD2 expression is likely to be involved in increased survival.