Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line

• Published in: Cell research Vol. 16; no. 4; pp. 356 - 366
• Main Authors: Wang, Xiao Xia, Liu, Rong, Jin, Shun Qian, Fan, Fei Yue, Zhan, Qi Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2006; Nature Publishing Group
• Subjects: Apoptosis - drug effects; Apoptosis - radiation effects; Apoptosis Regulatory Proteins - genetics; Aurora Kinases; Biomedical and Life Sciences; Caspase 3; Caspases - metabolism; Cell Biology; Cell Line, Tumor; Cell Proliferation; Cisplatin - antagonists & inhibitors; Esophageal Neoplasms - genetics; Humans; Irradiation; Life Sciences; Neoplasms, Squamous Cell - genetics; Neoplasms, Squamous Cell - metabolism; Neoplastic Stem Cells; original-article; Poly(ADP-ribose) Polymerases - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Radiation Tolerance - genetics; RNA Interference - drug effects; RNA Interference - radiation effects; RNA, Small Interfering - drug effects; RNA, Small Interfering - genetics; RNA, Small Interfering - radiation effects; Transfection; Ultraviolet radiation; Ultraviolet Rays; 基因表达; 细胞增生; 肿瘤细胞; 食管细胞癌; apoptosis; esophageal squamous cell carcinoma (ESCC); PARP; siRNA; Aurora-A; caspase-3
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/sj.cr.7310046

Attrora-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 Attrora-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 Attrora-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 （ADPribose） polymerase （PARP） in Attrora-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.