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

被引：28

作者：

Baldini, Enke ^{[1
]}

Arlot-Bonnemains, Yannick ^{[2
]}

Sorrenti, Salvatore ^{[3
]}

Mian, Caterina ^{[4
]}

Pelizzo, Maria R. ^{[4
]}

De Antoni, Enrico ^{[3
]}

Palermo, Silvio ^{[3
]}

Morrone, Stefania ^{[1
]}

Barollo, Susi ^{[5
]}

Nesca, Angela ^{[1
]}

Moretti, Costanzo G. ^{[6
]}

D'Armiento, Massimino ^{[1
]}

Ulisse, Salvatore ^{[1
]}

机构：

[1] Sapienza Univ Rome, Dept Expt Med, Rome, Italy

[2] Univ Rennes 1, UMR Genet & Dev 6061, IFR GFAS 140, Fac Med,CNRS, Rennes, France

[3] Sapienza Univ Rome, Dept Surg Med, Rome, Italy

[4] Univ Padua, Dept Med & Surg Sci, Padua, Italy

[5] IRCCS, Veneto Inst Oncol IOV, Padua, Italy

[6] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy

来源：

BMC CANCER | 2011年 / 11卷

关键词：

NUCLEAR-DNA CONTENT; MITOTIC PHOSPHORYLATION; HISTONE H3; A KINASE; CANCER; OVEREXPRESSION; SURVIVAL; VX-680; RET; LOCALIZATION;

D O I：

10.1186/1471-2407-11-411

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: 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. Methods: 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. Results: 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. Conclusions: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment.

引用

页数：12

共 56 条

[21] VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo [J].