Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT
1 Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
2 CNRS-UMR 6061 "Génétique et Développement", IFR 140 G.F.A.S., Faculté de Médecine, Université Rennes 1, Rennes, France
3 Department of Surgical Sciences, "Sapienza" University of Rome, Rome, Italy
4 Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
5 Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
6 Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy
BMC Cancer 2011, 11:411 doi:10.1186/1471-2407-11-411Published: 26 September 2011
The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets.
The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy.
The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar.
We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment.