Alteration of REDD1-mediated mammalian target of rapamycin pathway and hypoxia-inducible factor-1α regulation in human breast cancer

Ja Seung Koo, Woohee Jung

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)289-300
Number of pages12
JournalPathobiology
Volume77
Issue number6
DOIs
Publication statusPublished - 2011 Jan 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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