mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.
AffiliationUCD School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin, Ireland.
TOR Serine-Threonine Kinases/metabolism
TOR Serine-Threonine Kinases
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CitationmTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors. 2012, 21 (2):178-82 Breast
JournalBreast (Edinburgh, Scotland)
AbstractTriple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.
- Alteration of REDD1-mediated mammalian target of rapamycin pathway and hypoxia-inducible factor-1α regulation in human breast cancer.
- Authors: Koo JS, Jung W
- Issue date: 2010
- Phosphorylated mTOR expression correlates with poor outcome in early-stage triple negative breast carcinomas.
- Authors: Ueng SH, Chen SC, Chang YS, Hsueh S, Lin YC, Chien HP, Lo YF, Shen SC, Hsueh C
- Issue date: 2012
- Efficacy of everolimus, a novel mTOR inhibitor, against basal-like triple-negative breast cancer cells.
- Authors: Yunokawa M, Koizumi F, Kitamura Y, Katanasaka Y, Okamoto N, Kodaira M, Yonemori K, Shimizu C, Ando M, Masutomi K, Yoshida T, Fujiwara Y, Tamura K
- Issue date: 2012 Sep
- [Clinicopathologic features and prognosis of triple negative breast cancer].
- Authors: Zhou T, Yang L, Ma GM, Li CX, Bai Y, Zhao JA, Wang XL, Geng CZ
- Issue date: 2009 Aug 25
- Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization.
- Authors: Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, Schnall M, Alavi A
- Issue date: 2008 Mar 1
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