title: 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.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
authors.forename: Yannick
authors.initials: Y
authors.lastname: Arlot-Bonnemains
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sorrenti
authors.forename: Caterina
authors.initials: C
authors.lastname: Mian
authors.forename: Maria R
authors.initials: MR
authors.lastname: Pelizzo
authors.forename: Enrico
authors.initials: E
authors.lastname: De Antoni
authors.forename: Silvio
authors.initials: S
authors.lastname: Palermo
authors.forename: Stefania
authors.initials: S
authors.lastname: Morrone
authors.forename: Susi
authors.initials: S
authors.lastname: Barollo
authors.forename: Angela
authors.initials: A
authors.lastname: Nesca
authors.forename: Costanzo G
authors.initials: CG
authors.lastname: Moretti
authors.forename: Massimino
authors.initials: M
authors.lastname: D'Armiento
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ulisse
mesh_terms: D000328:Adult; D000368:Aged; D064127:Aurora Kinases; D018278:Carcinoma, Neuroendocrine; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010766:Phosphorylation / Q000187:drug effects; D011003:Ploidies; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D021381:Protein Transport / Q000187:drug effects; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D008941:Spindle Apparatus / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D006657:Histones; D047428:Protein Kinase Inhibitors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases