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高迁移率族蛋白B1和丝裂原活化蛋白激酶激活的蛋白激酶2在吉西他滨耐药的胰腺癌细胞中上调。

High-mobility Group Box 1 and Mitogen-activated Protein Kinase activated Protein Kinase-2 Are Up-regulated in Gemcitabine-resistant Pancreatic Cancer Cells.

作者信息

Kuramitsu Yasuhiro, Wang Yufeng, Kitagawa Takao, Tokuda Kazuhiro, Akada Junko, Tokunaga Masayuki, Nakamura Kazuyuki

机构信息

Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.

出版信息

Anticancer Res. 2015 Jul;35(7):3861-5.

Abstract

BACKGROUND

Results of our previous studies demonstrated that the expression of heat-shock protein 27 (HSP27) was increased and HSP27 was phosphorylated in the GEM-resistant pancreatic cancer cell line, KLM1-R. The expression of HSP27 is regulated mainly by heat-shock factor 1, but other transcription factors or kinases have been reported to activate HSP27. High-mobility group box 1 (HMGB1) is a nuclear transcription factor. It has been reported that HMGB1 regulates HSP27 gene expression. Mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK2) phosphorylates HSP27. In the present study, we investigated the expression of HMGB1 and MAPKAPK2 in KLM1-R cells.

MATERIALS AND METHODS

The expression levels of HMGB1 and MAPKAPK2 were compared between KLM1 and KLM1-R cells by western blotting.

RESULTS

The protein expression of both HMGB1 and MAPKAPK2 were increased in KLM1-R cells compared to KLM1 cells.

CONCLUSION

The increase of both HMGB1 and MAPKAPK2 in KLM1-R cells compared to KLM1 suggest the possibility of the activation of the pathway of HSP27 by HMGB1 and MAPKAPK2 in gemcitabine-resistant KLM1-R cells.

摘要

背景

我们之前的研究结果表明,在吉西他滨耐药的胰腺癌细胞系KLM1-R中,热休克蛋白27(HSP27)的表达增加且HSP27发生了磷酸化。HSP27的表达主要受热休克因子1调节,但据报道其他转录因子或激酶也可激活HSP27。高迁移率族蛋白B1(HMGB1)是一种核转录因子。据报道,HMGB1可调节HSP27基因的表达。丝裂原活化蛋白激酶激活的蛋白激酶2(MAPKAPK2)可使HSP27磷酸化。在本研究中,我们调查了KLM1-R细胞中HMGB1和MAPKAPK2的表达情况。

材料与方法

通过蛋白质印迹法比较了KLM1和KLM1-R细胞中HMGB1和MAPKAPK2的表达水平。

结果

与KLM1细胞相比KLM1-R细胞中HMGB1和MAPKAPK2的蛋白表达均增加。

结论

与KLM1相比,KLM1-R细胞中HMGB1和MAPKAPK2均增加,提示在吉西他滨耐药的KLM1-R细胞中,HMGB1和MAPKAPK2可能激活HSP27途径。

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