SciELO - Scientific Electronic Library Online

 
vol.51 issue5Molecular genetics of papillary thyroid carcinoma: great expectations...The importance of sodium/iodide symporter (NIS) for thyroid cancer management author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Arquivos Brasileiros de Endocrinologia & Metabologia

Print version ISSN 0004-2730

Abstract

GARCIA-JIMENEZ, Custodia  and  SANTISTEBAN, Pilar. TSH signalling and cancer. Arq Bras Endocrinol Metab [online]. 2007, vol.51, n.5, pp. 654-671. ISSN 0004-2730.  http://dx.doi.org/10.1590/S0004-27302007000500003.

Thyroid cancers are the most frequent endocrine neoplasms and mutations in the thyrotropin receptor (TSHR) are unusually frequent. Here we present the state-of-the-art concerning the role of TSHR in thyroid cancer and discuss it in light of the cancer stem cell theory or the classical view. We briefly review the gene and protein structure updating the cancer related TSHR mutations database. Intriguingly, hyperfunctioning TSHR mutants characterise differentiated cancers in contrast to undifferentiated thyroid cancers which very often bear silenced TSHR. It remains unclear whether TSHR alterations in thyroid cancers play a role in the onset or they appear as a consequence of genetic instability during evolution, but the presence of functional TSHR is exploited in therapy. We outline the signalling network build up in the thyrocyte between TSHR/PKA and other proliferative pathways such as Wnt, PI3K and MAPK. This network’s integrity surely plays a role in the onset/evolution of thyroid cancer and needs further research. Lastly, future investigation of epigenetic events occurring at the TSHR and other loci may give better clues for molecular based therapy of undifferentiated thyroid carcinomas. Targeted demethylating agents, histone deacetylase inhibitors combined with retinoids and specific RNAis may help treatment in the future.

Keywords : Thyrotropin; Cancer; Signalling; MAPK; PI3K; PKA; Wnt; Thyroid; NIS.

        · abstract in Portuguese     · text in English     · pdf in English