Aurora-A kinase has been shown to be deregulated in thyroid cancer cells and tissues (Int J Cancer 119:275-282, 2006). Among the Aurora-A substrates identified, TACC3, a member of the Transforming Acidic Coiled-Coil family, has been shown to play a role in cell cycle progression. Moreover, alterations of TACC3 expression occur in several cancer types. Despite that, its expression in normal or transformed human thyrocytes has not been investigated. In the present study, we first demonstrated the expression of the TACC3 gene in normal human thyrocytes (HTU5) and showed that it is modulated in a cell cycle dependent manner. Experiment of immunoprecipitation from human thyrocytes cell protein extracts demonstrated that Aurora-A and TACC3 interact in vivo, while experiments of indirect immunofluorescence showed that TACC3 and Aurora-A co-localize in the proximity of the centrosome onto the spindle microtubules. We next demonstrated that the levels of TACC3 mRNA and protein were, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP) and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated human thyroid cancer tissues TACC3 mRNA levels were found, with respect to normal matched tissues, reduced in 56% of cases by 0.50±0.07 fold (p<0.01) and increased in 44% of cases by 1.96±0.35 fold (p<0.05). In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs could be demonstrated (r=0.717, p<0.01). In conclusions, we demonstrated that TACC3 gene is expressed in human thyroid cells in a cell cycle dependent manner, and that the protein is localized onto the spindle microtubules where it interacts with Aurora-A. Along with the observation that TACC3 and Aurora-A expression varied together in human thyroid cancer tissues, we suggest that these proteins may serve similar functions and that deregulation of one or both gene expression may led to thyroid cancer aneuploidy.
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|Titolo:||Transforming acid coiled-coil 3 and aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues.|
|Data di pubblicazione:||2007|
|Appartiene alla tipologia:||04d Abstract in atti di convegno|