Alteration of REDD1-Mediated Mammalian Target of Rapamycin Pathway and Hypoxia-Inducible Factor-1 alpha Regulation in Human Breast Cancer

作者：Koo Ja Seung; Jung Woohee^*

来源：Pathobiology, 2010, 77(6): 289-300.

DOI：10.1159/000320936

• Hypoxia
• REDD1
• Mammalian target of rapamycin
• Hypoxia-inducible factor-1 alpha
• Breast neoplasm

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)-1 alpha, REDD1, AMPK (5'-adenosine-monophosphate-activated protein kinase) alpha(1), 14-3-3 sigma, 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-1 alpha 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-1 alpha stabilization by downregulation of REDD1.

• 出版日期2010