The Mechanism Research Of Tyrosine Threonine Kinase Promotes Tumor Growth In Human Endometrioid Endometrial Adenocarcinoma

Objective: Endometrial cancer is the most common gynecologic malignancy,about 80% of which is endometrial endometrioid carcinoma(EEC).Aberrant expression and altered functions of spindle assembly checkpoint(SAC)protein play vital roles in many aspects of tumor development and progression.The purpose of this study was to explore the oncogenic functions and underlying mechanisms of a SAC-related protein,TTK protein kinase,in EEC tumorigenesis and progression.Methods: First TTK expression was detected in EEC tissues compared to normal endometrium as control,by qRT-PCR,western-blot as well as immunohistochemistry.Then,loss function of TTK was attributed in two EEC cell lines by RNA interference,and cell proliferation was determined by MTS,Ki67 staining and PH3 staining.Cell cycle and cell apoptosis were examined by flow cytometry and western blot.Results: We demonstrated that TTK was upregulated in EEC cell linesand primary tumors;and its expression was associated with tumor stages.Depletion of TTK inhibited EEC cell proliferation and promoted cell apoptosis.Mechanistic study revealed that knockdown of TTK induced EEC cell G2 arrest and triggered caspase-dependent cell apoptosis.Conclusions: TTK is significantly upreguated in EEC and its function is critical for EEC cell proliferation and cell apoptosis.Therefore it may serve as a potential intervention target.