ANALYSIS OF MAP-KINASE IN THE BLADDER CANCER AND TARGETED MOLECULAR STRATEGIES BASED ON THE BLOCKADE OF THE MAP-KINASE PATHWAYS

膀胱癌中MAP激酶的分析及基于MAP激酶途径阻断的靶向分子策略

• 批准号: 18591773
• 负责人: SHISHIDO Toshishide
• 金额: $ 2.21万
• 依托单位: Kyorin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591773/
• 关键词: baldder cancer; MAPK; Elk-1; MEK; ERK; MEK inhivitor

Background: The mitogen-activated protein kinase (MAPK) cascade plays a crucial role in the transduction of extra cellular signals into responses governing growth and differentiation. The effects of a specific inhibitor of the MAPK kinase pathway on inhibition of urothelial cancer cell cycle-dependent kinases have been examined. Materials and Methods: We evaluated the expression of Elk-1 mRNA in 15 normal urine samples or 20 urine sample of the patient with bladder cancer, and 20 normal urothelial or 40 bladder cancer specimens. We investigated inhibition effect of MAPK activation in bladder cancer by studying the effect of MEK1/2 inhibitor on a panel of six human urothelial carcinoma cell lines. Results: Elk-1 mRNAexpression was not detected in any of the normal urine samples and normal urothelial mucosa. In the other, Elk-1 mRNA expressed all of the human transitional cell carcinoma cell lines, 20.0% urine sample of the patient with bladder cancer and 70.0% bladder cancer specimens. No relations were observed between the Elk-1 mRNA expression and pathological grade or staging in bladder cancer specimens. Several TUNEL positive cells were present in specimens 6 bladder cancer cells treated with MEK1/2 inhibitor. The expression level of the MAPK pathway in six bladder cancer cell lines using MAPK phosphorylation assay were various. The MEK inhibitor induced slightly apoptosis in UC cell lines by TUNEL methods, but not inhibited phosphorylation of MAPK in the MAPK Assays. Conclusions: Only MAPK phosphorylation may not contribute to carcinogenesis and tumor proliferation in the bladder cancer. As a result, activation of Elk-1 in nucleus may contribute to carcinogenic transformation rather than in tumor progression.

背景：丝裂原激活蛋白激酶 (MAPK) 级联在细胞外信号转导为控制生长和分化的反应中发挥着至关重要的作用。已经检查了 MAPK 激酶途径的特定抑制剂对尿路上皮癌细胞周期依赖性激酶的抑制作用。材料和方法：我们评估了 15 份正常尿液​​样本或 20 份膀胱癌患者尿液样本以及 20 份正常尿路上皮或 40 份膀胱癌样本中 Elk-1 mRNA 的表达。我们通过研究 MEK1/2 抑制剂对六种人类尿路上皮癌细胞系的影响，研究了膀胱癌中 MAPK 激活的抑制作用。结果：在所有正常尿液样本和正常尿路上皮粘膜中均未检测到Elk-1 mRNA表达。另一方面，Elk-1 mRNA在所有人类移行细胞癌细胞系、20.0%膀胱癌患者尿液样本和70.0%膀胱癌标本中表达。在膀胱癌标本中未观察到Elk-1 mRNA 表达与病理分级或分期之间的关系。用MEK1/2抑制剂处理的6个膀胱癌细胞样本中存在一些TUNEL阳性细胞。 MAPK磷酸化检测显示六种膀胱癌细胞系中MAPK通路的表达水平存在差异。通过 TUNEL 方法，MEK 抑制剂诱导 UC 细胞系轻微凋亡，但在 MAPK 测定中不抑制 MAPK 磷酸化。结论：仅MAPK磷酸化可能不会导致膀胱癌的癌变和肿瘤增殖。因此，细胞核中Elk-1的激活可能有助于致癌转化而不是肿瘤进展。