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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Breast Neoplasms, Carcinoma, Ductal, Breast, Cell Cycle Proteins, Gene Expression Regulation, Neoplastic, Genes, p53, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Lymph Nodes, Neoplasm Invasiveness, Neoplasm Staging, Receptors, Estrogen, Transcription Factors.
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Are expression of hypoxia-inducible factor-1alpha and cell cycle proteins in invasive breast cancer estrogen receptor related? Context: 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 between p21 and HIF-1alpha (P = 0.105) in the whole group of patients. However, the subgroup of ER-positive cancers was characterized by a strong positive association between HIF-1alpha and p21 (P = 0.023), and HIF-1alpha lacked any relation with proliferation.
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HIF-1alpha overexpression is associated with increased proliferation, which might explain the adverse prognostic impact of increased concentrations of HIF-1alpha in invasive breast cancer. In ER-positive tumors, HIF-1alpha is associated with p21 but not against proliferation. This shows the importance of further functional analysis to unravel the role of HIF-1 in late cell cycle progression, and the link between HIF-1, p21, and ER. Final Decision: yes