title: Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line.
abstract: Aurora-A kinase, a serine/threonine protein kinase, is a potential oncogene. Amplification and overexpression of Aurora-A have been found in several types of human tumors, including esophageal squamous cell carcinoma (ESCC). It has been demonstrated that cells overexpressing Aurora-A are more resistant to cisplatin-induced apoptosis. However, the molecular mechanisms mediating these effects remain largely unknown. In this report, we showed that overexpression of Aurora-A through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin- or UV irradiation-induced apoptosis. Cleavages of caspase-3 and poly (ADP-ribose) polymerase (PARP) in Aurora-A overexpressing cells were substantially reduced after cisplatin or UV treatment. Furthermore, we found that silencing of endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells. In parallel, overexpression of Aurora-A potently upregulated the expression of Bcl-2. Moreover, the knockdown of Bcl-2 by siRNA abrogated the Aurora-A's effect on inhibiting apoptosis. Taken together, these data provide evidence that Aurora-A overexpression promoting cell proliferation and inhibiting apoptosis, suggesting a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of ESCC cells.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Xiao Xia
authors.initials: XX
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Shun Qian
authors.initials: SQ
authors.lastname: Jin
authors.forename: Fei Yue
authors.initials: FY
authors.lastname: Fan
authors.forename: Qi Min
authors.initials: QM
authors.lastname: Zhan
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D064127:Aurora Kinases; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000037:antagonists & inhibitors; D004938:Esophageal Neoplasms / Q000235:genetics*; D006801:Humans; D018307:Neoplasms, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D011836:Radiation Tolerance / Q000235:genetics; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011065:Poly(ADP-ribose) Polymerases; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin