The Role Of Aurora A Involving The Proliferation And Invasion Potential Of Endometrial Carcinoma

The family of Aurora represents a family of serine/threonine kinases,which stay highly conserved during evolution process among many species and regulate cell cycle progression orderly.Aurora kinases involve many procedures of cellular mitosis,their intercellular distribution,gene expression level and inner kinase activity vary strictly with cell cycles,accompanied by close interaction with many tumor suppressor gene,such as p53,BRCA2 and so on.Aurora A kinase is proved to be overexpressed in a variety of solid tumors including gynecological carcinomas such as endometrial carcinoma and ovarian carcinoma,of which Aurora A kinase closely relates to the formation,progression and prognosis.However,there are up till now only few researches which clearly illustrate and clarify the underlying molecular mechanisms that the family of Aurora kinases participate and promote malignant behaviours of endometrial carcinoma,such as locally invasion and distant metastasis.Our research have verified that in endometrial carcinoma,the highly important member of Aurora kinases family,Aurora A kinase,was significantly overexpressed at both protein and mRNA expression levels,compared to normal endometrial tissue,revealing the crucial role of Aurora A kinase in the carcinogenesis and development of endometrial carcinoma.After overexpressed Aurora A by infecting endometrial carcinoma cell lines Ishikawa and HEC-1B with the adenovirus-GFP-Aurora A,the proliferation rate of Ishikawa and HEC-1B increased to 1.43 fold(40MOI),1.75 fold(80MOI)(*P<0.05)and 1.48 fold(40MOI),1.70 fold(80MOI),respectively.While knocking down endogenous Aurora A using the si-RNA targeting Aurora A,the proliferation rate of Ishikawa and HEC-1B decreased to 72%and 69%,respectively(*P<0.05).Subsequently we apply the Transwell assay、Western Blotting and gletine zymography assay to study whether Aurora A could affect the invasion potential of endometrial cancer cell lines,results revealed that after infected by the adenovirus-GFP-Aurora A,the invasion potential of Ishikawa and HEC-1B increased by 1.73 and 1.97 fold respectively,compared to the corresponding control,while knockdown of Aurora A by transfecting the si-RNA targeting Aurora A,the invasion potential decreased by 26%and 30%(*P<0.05)respectively.Meanwhile,overexpression of Aurora A obviously up-regulated the protein expression levels and their proteinase activities of MMP-2 and MMP-9 in HEC-1B cell,as well as MMP-2 within Ishikawa cell.Further study revealed that Aurora A both phosphorylated the 308th threonine(T308)amino acid site,rather than the serine 473(S473)amino acid site within both Ishikawa and HEC-1B,while the inhibitor of PI3K/AKT pathway-LY294002 could decreased the positive regulation effect of Aurora A upon MMP-2 and MMP-9 of endometrial cell lines.In summary,our research supports that Aurora A is highly expressed in endometrial cancer tissues.Aurora A functions as a typical oncogene to enhanced the proliferation,migration and invasion potential of Ishikawa and HEC-1B,revealing that Aurora A kinase could be treated as a promising cure target for the development of targeted therapies of endometrial cancer.