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.

LENTINI L, AMATO A, SCHILLACI T, INSALACO L, & DI LEONARDO A (2008). Aurora-A transcriptional silencing and Vincristine treatment show a synergistic effect in human tumor cells. ONCOLOGY RESEARCH, 17, 115-125.

Aurora-A transcriptional silencing and Vincristine treatment show a synergistic effect in human tumor cells

LENTINI, Laura;AMATO, Angela;SCHILLACI, Tiziana;INSALACO, Lavinia;DI LEONARDO, Aldo
2008

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.
Settore BIO/18 - Genetica
LENTINI L, AMATO A, SCHILLACI T, INSALACO L, & DI LEONARDO A (2008). Aurora-A transcriptional silencing and Vincristine treatment show a synergistic effect in human tumor cells. ONCOLOGY RESEARCH, 17, 115-125.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/35639
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