1. Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells
- Author
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Laura Lentini, Tiziana Schillaci, Angela Amato, L. Insalaco, Aldo Di Leonardo, LENTINI L, AMATO A, SCHILLACI T, INSALACO L, and DI LEONARDO A
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Transcription, Genetic ,Apoptosis ,macromolecular substances ,Protein Serine-Threonine Kinases ,Biology ,Transfection ,PLK1 ,Aurora Kinases ,RNA interference ,Cell Line, Tumor ,medicine ,Humans ,Gene silencing ,Gene Silencing ,RNA, Small Interfering ,Mitotic catastrophe ,Centrosome ,Cisplatin ,Carcinoma ,Cell Cycle ,Drug Synergism ,AuroraA/stk15,centrosome amplification,Aneuploidy, CIN ,General Medicine ,Cell cycle ,Aneuploidy ,Antineoplastic Agents, Phytogenic ,Gene Expression Regulation, Neoplastic ,Settore BIO/18 - Genetica ,enzymes and coenzymes (carbohydrates) ,Oncology ,Vincristine ,Colonic Neoplasms ,embryonic structures ,Cancer cell ,Cancer research ,biological phenomena, cell phenomena, and immunity ,HeLa Cells ,medicine.drug - Abstract
Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G 2 /M cell cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide-, and paclitaxel-induced apoptosis.Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of human colon cancer. Aneuploidy was also observed after Aurora-A ectopic overexpression in colon cancer cells with MIN phenotype. Silencing of Aurora-A by RNA interference in tumor cell lines triggered arrest of the cell cycle associated to apoptosis/ mitotic catastrophe. Finally, Aurora-A transcriptional silencing seems to confer cancer cells a greater sensitivity to chemotherapy by vincristine, indicating Aurora-A as a possible gene target in cancer therapy.
- Published
- 2008
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