Downregulation of tyrosine threonine kinase inhibits tumor growth via G2/M arrest in human endometrioid endometrial adenocarcinoma.

Abstract

Endometrial cancer is the most common gynecologic malignancy, about 80% of which is endometrial endometrioid carcinoma. Dysregulation of spindle assembly checkpoint plays a vital role in endometrial endometrioid carcinoma tumorigenesis and progression. The purpose of this study was to explore how tyrosine threonine kinase, a spindle assembly checkpoint-related protein, promotes the endometrial endometrioid carcinoma progression. We found that both messenger RNA and protein levels of tyrosine threonine kinase in endometrial endometrioid carcinoma tissues are higher than those in normal endometrial tissues, and its expression is associated with tumor stages. Genetic depletion of tyrosine threonine kinase by RNA interference in two endometrial endometrioid carcinoma cell lines significantly inhibits cell proliferation and induces apoptosis. Mechanistically, depletion of tyrosine threonine kinase induces G2/M cell cycle arrest and triggers caspase-dependent cell apoptosis. Collectively, tyrosine threonine kinase is significantly upregulated in endometrial endometrioid carcinoma, and downregulation of tyrosine threonine kinase can suppress endometrial endometrioid carcinoma cell proliferation and promote apoptosis via G2/M cell cycle arrest. Our study demonstrates that tyrosine threonine kinase can be a potential therapeutic target for endometrial endometrioid carcinoma treatment.

• Authors: Jiamiao Zhang, Yan Jiang, Yu Zhao, Wanxue Wang, Yiran Xie, Huating Wang, Yihua Yang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 39 Issue 7 Pg. 1010428317712444 (Jul 2017) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 28718377 (Publication Type: Journal Article)

Chemical References

• Protein Kinase Inhibitors
• Protein-Tyrosine Kinases
• Protein Serine-Threonine Kinases

Topics

• Adenocarcinoma (drug therapy, genetics, pathology)
• Apoptosis (drug effects)
• Carcinoma, Endometrioid (drug therapy, genetics, pathology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Endometrial Neoplasms (drug therapy, genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• M Phase Cell Cycle Checkpoints (drug effects)
• Neoplasm Staging
• Protein Kinase Inhibitors (administration & dosage)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics)
• Protein-Tyrosine Kinases (antagonists & inhibitors, genetics)
• RNA Interference