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Androgen Receptor Promotes Gastric Carcinogenesis via Upregulating Cell Cycle-Related Kinase Expression.


ABSTRACT: Gastric cancer (GC) is a leading global health problem as it is the fifth most common cancer type and the third most common cause of cancer-related deaths worldwide. In most areas of the world, the incidence rate of GC is 1.5- to 3-fold higher in males than in females. The androgen receptor (AR) is an independent adverse prognostic factor in patients with GC. However, the mechanism by which AR regulates the progression of GC remains unclear. In this study, we found that AR expression was upregulated in 6/8 GC cell lines, and this expression was higher than that in immortalized gastric cells. AR expression was also higher in GC tissues than in adjacent tissues. Moreover, the ectopic expression of AR promoted the colony formation ability, migration and invasion of GC cells. In contrast, AR knockdown had the opposite effects on GC cell lines. Remarkably, we found that AR regulated cell cycle-related kinase (CCRK) expression through transcriptional mechanisms. The AR-CCRK axis promoted GC development through the phosphorylation of GSK3? and ?-catenin. Furthermore, TCGA data revealed that high expression of AR or CCRK was related to poor prognosis in GC patients. The prognosis was significantly worse in patients with concurrent high AR and CCRK expression than in patients with low AR and CCRK expression. In conclusion, our study demonstrated that AR and CCRK acted as oncogenes in GC progression. However, their clinical roles require further exploration.

SUBMITTER: Wang R 

PROVIDER: S-EPMC6691715 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Androgen Receptor Promotes Gastric Carcinogenesis via Upregulating Cell Cycle-Related Kinase Expression.

Wang Ren R   Xu Xiao-Yi XY   Zhu Hong H   Liang Xiong X   Li Xue X   Jia Ming-Xu MX   Wang Qing-Hua QH   Wang Hui-Yun HY   Li Xiao-Xing XX   Zhao Gui-Jun GJ  

Journal of Cancer 20190710 18


Gastric cancer (GC) is a leading global health problem as it is the fifth most common cancer type and the third most common cause of cancer-related deaths worldwide. In most areas of the world, the incidence rate of GC is 1.5- to 3-fold higher in males than in females. The androgen receptor (AR) is an independent adverse prognostic factor in patients with GC. However, the mechanism by which AR regulates the progression of GC remains unclear. In this study, we found that AR expression was upregul  ...[more]

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