Expression of hypoxia-inducible factor-1alpha and cell cycle proteins in invasive breast cancer are estrogen receptor related

Breast Cancer Research : BCR
R BosElsken van der Wall

Abstract

The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key regulator of the cellular response to hypoxia. Previous studies showed that concentrations of its subunit HIF-1alpha, as a surrogate for HIF-1 activity, are increased during breast carcinogenesis and can independently predict prognosis in breast cancer. During carcinogenesis, the cell cycle is progressively deregulated, and proliferation rate is a strong prognostic factor in breast cancer. In this study we undertook a detailed evaluation of the relationships between HIF-1alpha and cell cycle-associated proteins. In a representative estrogen receptor (ER) group of 150 breast cancers, the expression of HIF-1alpha, vascular endothelial growth factor, the ER, HER-2/neu, Ki-67, cyclin A, cyclin D1, p21, p53, and Bcl-2 was investigated by immunohistochemistry. High concentrations (5% or more) of HIF-1alpha were associated with increased proliferation as shown by positive correlations with Ki-67 (P < 0.001) and the late S-G2-phase protein cyclin A (P < 0.001), but not with the G1-phase protein cyclin D1. High HIF-1alpha concentrations were also strongly associated with p53 positivity (P < 0.001) and loss of Bcl-2 expression (P = 0.013). No association was found betwe...Continue Reading

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Citations

Nov 9, 2012·The Journal of Membrane Biology·Izabela DobrzyńskaZbigniew A Figaszewski
Nov 22, 2007·Breast Cancer Research and Treatment·Petra van der GroepPaul J van Diest
Jun 23, 2009·Journal of Clinical Pathology·P van der GroepE van der Wall
Oct 17, 2008·Breast Cancer Research : BCR·Joshua Marshall ThornburgJason Chesney
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Methods Mentioned

BETA
dissection
co-immunoprecipitation

Software Mentioned

SPSS
Histoscore

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