SERPINA3 promotes endometrial cancer cells growth by regulating G2/M cell cycle checkpoint and apoptosis

Endometrial carcinoma (EC) is the most common gynecologic cancer worldwide and is one of the leading causes of death in women. Therefore, it is urgent to elucidate the pathological mechanisms of EC. SERPINA3 is a member of the serpin super-family of protease inhibitors. Its aberrant expression has b...

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Bibliographic Details
Published in:International journal of clinical and experimental pathology 2014-01, Vol.7 (4), p.1348-1358
Main Authors: Yang, Guang-Dong, Yang, Xiao-Mei, Lu, Huan, Ren, Yuan, Ma, Ming-Ze, Zhu, Lin-Yan, Wang, Jing-Hao, Song, Wei-Wei, Zhang, Wen-Ming, Zhang, Rong, Zhang, Zhi-Gang
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Apoptosis - physiology
Cell Cycle Checkpoints - physiology
Cell Line, Tumor
Cell Proliferation - physiology
Endometrial Neoplasms - pathology
Endometrial Neoplasms - physiopathology
Female
G2 Phase Cell Cycle Checkpoints - physiology
Humans
In Vitro Techniques
M Phase Cell Cycle Checkpoints - physiology
MAP Kinase Signaling System - physiology
Middle Aged
Mitogen-Activated Protein Kinase Kinases - physiology
Neoplasm Staging
Original
Phosphatidylinositol 3-Kinases - physiology
Proto-Oncogene Proteins c-akt - physiology
Serpins - physiology
Signal Transduction - physiology
Up-Regulation - physiology
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Summary:Endometrial carcinoma (EC) is the most common gynecologic cancer worldwide and is one of the leading causes of death in women. Therefore, it is urgent to elucidate the pathological mechanisms of EC. SERPINA3 is a member of the serpin super-family of protease inhibitors. Its aberrant expression has been observed in various tumor cells. However, its clinical significance and biological function in endometrial cancer remains unknown. In the present study, we demonstrated that SERPINA3 expression was significantly up-regulated in EC samples and was closely correlated with lower differentiation, higher stage, positive lymph node or vascular thrombosis and negative estrogen receptor (ER), indicating a poor prognosis. We then demonstrated that SERPINA3 promoted EC cells proliferation by regulating G2/M checkpoint in cell cycle and inhibited cells apoptosis, and we further uncovered that the pro-proliferative effect of SERPINA3 on EC was likely ascribed to the activation of MAPK/ERK1/2 and PI3K/AKT signaling. The results of our study may provide insight into the application of SERPINA3 as a novel predictor of clinical outcomes and a potential therapeutic target of EC.
ISSN:1936-2625