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http://dx.doi.org/10.7314/APJCP.2015.16.6.2495

Expression and Prognostic Role of MEKK3 and pERK in Patients with Renal Clear Cell Carcinoma  

Chen, Qi (Department of Clinical Laboratory, Taizhou Central Hospital)
Lu, Hong-sheng (Department of Pathology, Taizhou Central Hospital)
Gan, Mei-fu (Department of Pathology, Taizhou Hospital)
Chen, Lan-xi (Department of Pathology, Taizhou Central Hospital)
He, Kai (Department of Pathology, Taizhou Central Hospital)
Fan, Guang-min (Department of Pathology, Taizhou Central Hospital)
Cao, Xue-quan (Department of Pathology, Taizhou Central Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.6, 2015 , pp. 2495-2499 More about this Journal
Abstract
Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation, terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of RCCC and 28 control cases. Expression levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+ FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05). CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors.
Keywords
MEKK3; pERK; FoxP3; renal clear cell carcinoma; prognosis;
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1 Cao X, Lu H, Zhang L, et al (2014). MEKK3 and survivin expression in cervical cancer: association with clinicopathological factors and prognosis. Asian Pac J Cancer Prev, 15, 5271-76.   DOI
2 Christophe F, Sylvain M (2010). From basic research to clinical development of MEK 1/2 inhibitors for cancer therapy. J Hematol Oncol, 3, 3-8.   DOI
3 Chen L, Shi Y, Jiang CY, et al (2011). Expression and prog- nostic role of pan-Ras, Raf-1, pMEK1 and pERK1/2 in patients with hepatocellular carcinoma. EJSO, 37, 513-20   DOI
4 Cindy Neuzillet, Annemilai Tijeras-Raballand, Louis de Mestier, et al (2014). MEK in cancer and cancer therapy. Pharmacol Ther, 141, 160-71.   DOI
5 Craig EA, Stevens MV, Vaillancourt RR, et al (2008). MAP3Ks as central regulators of cell fate during development. Developmental Dynamics, 237, 3102-14.   DOI   ScienceOn
6 Escudier B, Eisen T, Stadler WM, et a1 (2007). SorMenib in advanced clear-cell renal-cell carcinoma. N Engl J Med, 356, l25-34.   DOI
7 Hanahan, D, Weinberg, RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.   DOI
8 Kamal S, Sherene L, Evandro de Azambuja, et al (2013). Targeting the PI3K/AKT/ mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev, 39, 935-46.   DOI
9 Lee HE, Park DJ, Kim WH, et a1 (2011). High FOXP3 regulatory t-cell density in the sentinel lymph node is associated with downstream non-sentinel lymph-node metastasis in gastric cancer. Br J Cancer, 34, 413-19.
10 Lu H, Cao X, Zhang H, et al (2014). Imbalance between MMP-2, 9 and TIMP-1 promote the invasion and metastasis of renal cell carcinoma via SKP2 signaling pathways. Tumor Biol, 35, 9807-13.   DOI
11 Lu H, Gan M, Zhang G, et al (2010). Expression of survivin, caspase-3 and p53 in cervical cancer assessed by tissue microarray: correlation with clinicopathology and prognosis. Eur J Gynaecol Oncol, 6, 662-66.
12 McCubrey JA, Steelman LS, Chappell WH, et al (2007). Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta, 1773, 1263-84.   DOI
13 Shinohara H, Yamasaki S, Maeda S, et a1 (2009). Regulation of NF-${\kappa}B$ dependent T cell activation and development by MEKK3. Int Immunol, 21, 393-401   DOI
14 Wang G, Liu G, Liu Y, et a1 (2012). FOXP3 expression in esophageal cancer cells is associated with poor prognosis in esophageal cancer. Hepatogastroenterol, 59, 2186-91.
15 Wang X, Chang X, Su B, et a1 (2009). MEKK3 is essential for lymphopenia induced T cell proliferation and survival. J Immunol, 6, 3597-608.
16 Yoshimura K, Uemura H (2013). Role of vaccine therapy for renal cell carcinoma in the era of targeted therapy. Int J Urol, 20, 744-55.   DOI
17 Zeng C, Yao Y, Jie W, et al (2013). Up-regulation of Foxp3 participates in progression of cervical cancer. Cancer Immunol Immunother, 3, 481-7.
18 Young A, Lou D, McCormick F (2013). Oncogenic and wild-type ras play divergent roles in the regulation of mitogen-activated protein kinase signaling. Cancer Discov, 1, 112-23.