Alteration of REDD1-Mediated Mammalian Target of Rapamycin Pathway and Hypoxia-Inducible Factor-1α Regulation in Human Breast CancerKoo J.S. · Jung W.
Department of Pathology, Yonsei University Health System, Seoul, South Korea
Dr. Woohee Jung, MD, PhD
Department of Pathology, Yonsei University Health System
Gangnam Severance Hospital
612 Eonjuro Gangnam-gu, Seoul 135-720 (South Korea)
Tel. +82 2 2019 3541, Fax +82 2 3463 2103, E-Mail Jungwh96@yuhs.ac
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Objective: The purpose of this study is to investigate REDD1-(regulated in development and DNA damage response 1) mediated regulation of the mammalian target of rapamycin (mTOR) pathway in breast cancer. Methods: A tissue microarray included samples from 224 patients with breast cancer, and 30 patients with papilloma were used as a control group. An immunohistochemistry (IHC) including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epithelial growth factor receptor, cytokeratin 5/6, glucose transporter 1 (Glut-1), hypoxia-inducible factor (HIF)-1α, REDD1, AMPK (5′-adenosine-monophosphate-activated protein kinase) α1, 14-3-3σ, phosphatase and tensin homolog, phospho-Akt, phospho-mTOR, phospho-S6, and Ki-67 was conducted. The phenotypic classification of breast cancer was performed based on the results of the IHC for ER, PR and HER2: luminal A, luminal B, HER2 overexpression and triple-negative breast cancer (TNBC). Results: Glut-1 and HIF-1α were more highly expressed in TNBC, the HER2 overexpression type and papilloma than in the luminal A and B phenotypes (p = 0.000). REDD1 expression was higher in papilloma than in breast cancer (p = 0.000), but no difference was found among the 4 breast cancer phenotypes (p = 0.307). Conclusion: In the HER2 overexpression type and TNBC, tumor cell proliferation and survival in the hypoxic tumor environment could possibly be due to disinhibition of the mTOR pathway and HIF-1α stabilization by downregulation of REDD1.
© 2011 S. Karger AG, Basel
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