ArticleThe American journal of pathology2010
Mammalian target of rapamycin (mTOR) regulates cellular proliferation and tumor growth in urothelial carcinoma.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
- Beyond diabetes mellitus: role of metformin in non-muscle-invasive bladder cancer.Singapore medical journal · 2022Trial
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Distinct molecular signatures of upper tract urothelial carcinoma in Southwestern Taiwan: implications for targeted therapy and disease progression.American journal of cancer research · 2025Article
- Targeted therapy of cancer stem cells: inhibition of mTOR in pre-clinical and clinical research.Cell death & disease · 2024Review
- Plasmacytoid urothelial carcinoma of the urinary bladder-A clinicopathological and molecular analysis of 52 cases.Human pathology · 2024Article
- Genomics and Immunomics in the Treatment of Urothelial Carcinoma.Current oncology (Toronto, Ont.) · 2022Review
- Bystander effects induced by the interaction between urothelial cancer cells and irradiated adipose tissue-derived stromal cells in urothelial carcinoma.Human cell · 2022Article
- Effect of rapamycin on aging and age-related diseases-past and future.GeroScience · 2021Review
- Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing.Cancer cell international · 2021Article
- Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer.Cancer cell international · 2020Review
- Metformin Augments Panobinostat's Anti-Bladder Cancer Activity by Activating AMP-Activated Protein Kinase.Translational oncology · 2019Article
- Nelfinavir and Ritonavir Kill Bladder Cancer Cells Synergistically by Inducing Endoplasmic Reticulum Stress.Oncology research · 2018Article
- Article
- Periostin suppressesOncology letters · 2017Article
- AMPKα Is Suppressed in Bladder Cancer through Macrophage-Mediated Mechanisms.Translational oncology · 2016Article
- Metformin induces degradation of mTOR protein in breast cancer cells.Cancer medicine · 2016Article
- mTOR inhibitors in urinary bladder cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Inhibition of epithelial-mesenchymal transition in bladder cancer cells via modulation of mTOR signalling.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.The American journal of pathology · 2016Article
- Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells.Drug design, development and therapy · 2016Article
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12 authors at 3 institutions in 1 country.
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Abstract
Mammalian target of rapamycin (mTOR) signaling has been associated with aggressive tumor growth in many cancer models, although its role in urothelial carcinoma (UCC) has not been extensively explored. Expression of phosphorylated mTOR (P-mTOR) and a downstream target, ribosomal S6 protein (P-S6), was identified in 74% (90/121) and 55% (66/121) of muscle-invasive UCCs, respectively. P-mTOR intensity and %positive cells were associated with reduced disease-specific survival (P = 0.04, P = 0.08, respectively). Moreover, P-mTOR intensity corresponded to increased pathological stage (P < 0.01), and mTOR activity was associated with cell migration in vitro. In addition, mTOR inhibition via rapamycin administration reduced cell proliferation in UCC cell lines RT4, T24, J82, and UMUC3 in a dose-dependent manner to 6% of control levels and was significant at 1 nmol/L in J82, T24, and RT4 cells (P < 0.01, P < 0.01, P = 0.03, respectively) and at 10 nmol/L in UMUC3 cells (P = 0.03). Reduced proliferation corresponded with reduced P-S6 levels by Western blot, and effects were ablated by pretreatment of cells with mTOR-specific siRNA. No effects of rapamycin on apoptosis were identified by TUNEL labeling or PARP cleavage. Administration of rapamycin to T24-xenografted mice resulted in a 55% reduction in tumor volume (P = 0.03) and a 40% reduction in proliferation (P < 0.01) compared with vehicle-injected mice. These findings indicate that mTOR pathway activation frequently occurs in UCC and that mTOR inhibition may be a potential means to reduce UCC growth.
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