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Integrating microarray data from thyroid tumours and from their in vitro models.
David Weiss
ULB - IRIBHM/IRIDIA
dweiss@ulb.ac.be

Abstract

Thyroid tumours are caused by the deregulation of biochemical signal transduction pathways. These signaling pathways are activated by extracellular molecules acting as chemical signals, resulting in the modulation of gene activity inside the cell. It seems then plausible that normal thyroid cells in culture stimulated by chemicals that activate a particular signal transduction pathway can provide models to better understand, and eventually, to design diagnostics and treatments for these pathologies. To test this hypothesis, our group at IRIBHM is using microarrays to monitor simultaneously the level of activation of practically all the genes in thyroid tumours and in their in vitro cell culture putative models. Statistical analysis has yielded a 300-gene signature characteristic of a change of genetic program in normal thyroid cells following the stimulation of the cyclic AMP signaling pathway by Thyroid Stimulating Hormone (TSH). Based on this signature, we show that hyper functional thyroid nodules, which are benign tumours, resemble long time-stimulated thyroid cells. As it is known that this pathway is chronically activated in these tumours, the analysis validates the in vitro cell culture system in general, on a comprehensive molecular basis. The analysis has validated a cell culture model of hyperfunctional thyroid nodules. Kinetic data on hundreds of genes important for normal thyroid function and involved in the pathogenesis of hyperfunctional thyroid nodules has been obtained.

Keywords

Thyroid tumours, biochemical signaling pathways, gene expression, microarrays, data mining, biological models

References

  1. Wilma C.G. van Staveren, David Weiss Solís, Laurent Delys, David Venet, Matteo Cappello, Guy Andry, Jacques E. Dumont, Frédéric Libert, Vincent Detours and Carine Maenhaut. Gene expression in TSH-treated human thyrocytes and autonomous adenomas: suppression of negative feedbacks in tumorigenesis, PNAS, . In press.