Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells

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RESEARCH PRODUCT

Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells

Laura Lentini Tiziana Schillaci Angela Amato L. Insalaco Aldo Di Leonardo

subject

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 Centrosome Colonic Neoplasms embryonic structures Cancer cell Cancer research biological phenomena cell phenomena and immunity HeLa Cells medicine.drug

description

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.

year	journal	country	edition	language
2008-08-02	Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics

https://doi.org/10.3727/096504008785055521