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
MetadataShow full item record
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
Showing items related by title, author, creator and subject.
Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cellsBurleigh, Susan C; van de Laar, Teun; Stroop, Corne JM; van Grunsven, Wout MJ; O'Donoghue, Niaobh; Rudd, Pauline M; Davey, Gavin P (2011-10-18)Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.
Steroid metabolism and excretion in severe anorexia nervosa: effects of refeeding.Wassif, Wassif S; McLoughlin, Declan M; Vincent, Royce P; Conroy, Simon; Russell, Gerald F M; Taylor, Norman F; Department of Clinical Biochemistry, King's College Hospital National Health Service Foundation Trust, London, United Kingdom. firstname.lastname@example.org (2011-05)To our knowledge, changes in steroid metabolism in subjects with anorexia nervosa (AN) after weight gain have not been elucidated.