Cell research, 2006-04, Vol.16 (4), p.356-366
2006
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- Autor(en) / Beteiligte
- Titel
- Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line
- Ist Teil von
- Cell research, 2006-04, Vol.16 (4), p.356-366
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2006
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1001-0602eISSN: 1748-7838DOI: 10.1038/sj.cr.7310046Titel-ID: cdi_proquest_miscellaneous_67853272
- Format
- –
- Schlagworte
- Apoptosis - drug effects, Apoptosis - radiation effects, Apoptosis Regulatory Proteins - genetics, Aurora Kinases, Caspase 3, Caspases - metabolism, Cell Line, Tumor, Cell Proliferation, Cisplatin - antagonists & inhibitors, Esophageal Neoplasms - genetics, Humans, Neoplasms, Squamous Cell - genetics, Neoplasms, Squamous Cell - metabolism, Neoplastic Stem Cells, 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 Rays, 基因表达, 细胞增生, 肿瘤细胞, 食管细胞癌