Aurora-A transcriptional silencing and vincristine treatment show a synergistic effect in human tumor cells.
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 G2/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
Laura
L
Dipartimento di Biologia Cellulare e dello Sviluppo A. Monroy, Università di Palermo, Viale delle Scienze, Palermo, Italy.
Amato
Angela
A
Schillaci
Tiziana
T
Insalaco
Lavinia
L
Di Leonardo
Aldo
A
D000782:Aneuploidy; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D064127:Aurora Kinases; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000737:chemistry / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014750:Vincristine / Q000008:administration & dosage
D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D014750:Vincristine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases