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
- Mammalian target of rapamycin
- Hypoxia-inducible factor-1α
- Breast neoplasm
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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
Received: June 28, 2010
Accepted after revision: September 3, 2010
Published online: January 24, 2011
Number of Print Pages : 12
Number of Figures : 3, Number of Tables : 6, Number of References : 30
Pathobiology (Exploring the basis of disease)
Vol. 77, No. 6, Year 2010 (Cover Date: January 2011)
Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015-2008 (Print), eISSN: 1423-0291 (Online)
For additional information: http://www.karger.com/PAT
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