ArticleBMC urology2011
Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival.
Article in BMC urology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line.Oncology letters · 2019Article
- Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma ManagementAsian Pacific journal of cancer prevention : APJCP · 2019Review
- More precise prediction in Chinese patients with penile squamous cell carcinoma: protein kinase CK2α catalytic subunit (CK2α) as a poor prognosticator.Oncotarget · 2017Article
- CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Cancer-type dependent expression of CK2 transcripts.PloS one · 2017Article
- Increased expression of protein kinase CK2α correlates with poor patient prognosis in epithelial ovarian cancer.PloS one · 2017Article
- Keratin 19 as a key molecule in progression of human hepatocellular carcinomas through invasion and angiogenesis.BMC cancer · 2016Article
- Targeted therapies in bladder cancer: an overview of in vivo research.Nature reviews. Urology · 2015Review
- Protein kinase CK2α catalytic subunit is overexpressed and serves as an unfavorable prognostic marker in primary hepatocellular carcinoma.Oncotarget · 2015Article
- The route to personalized medicine in bladder cancer: where do we stand?Targeted oncology · 2015Review
- Rationale for the design of an oncology trial using a generic targeted therapy multi‑drug regimen for NSCLC patients without treatment options (Review).Oncology reports · 2013Review
- ALKBH2, a novel AlkB homologue, contributes to human bladder cancer progression by regulating MUC1 expression.Cancer science · 2013Article
- [Protein kinase CK2 and human malignant tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2012Review
- Convergent synthesis and evaluation of (18)F-labeled azulenic COX2 probes for cancer imaging.Frontiers in oncology · 2012Article
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5 authors.
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Abstract
backgroundSurvival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo.
methodsCOX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells.
resultsTreatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes.
conclusionsCOX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.
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