Molecular mechanisms of action in TSH-mediated regulation of thyroid cancer

CINTHIA ROSEMBLIT; MARIA CELESTE DIAZ FLAQUE MC; JOHANNA A DÍAZ ALBUJA; MARIA LAURA BARREIRO ARCOS; FLORENCIA CAYROL; HELENA A STERLE ; MARIA M DEBERNARDI; ALEJANDRA PAULAZO; M ALICIA KLECHA ; CREMASCHI, GRACIELA A.

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAI, SAFIS; 2018

Sociedad Argentina de Investigaciones Clínicas

The incidence of thyroid cancer has increased significantly withinlast decades in Argentina as in the rest of the world. Thyroid stimulatinghormone (TSH) controls thyroid function by binding to TSHreceptor (TSHR) coupled to G protein. TSH hyperactivation couldbe involved in thyroid diseases and cancer. PKC, a serine/threonineprotein kinase, has been widely implicated in malignant transformation,cell survival, motility and invasion. Classical and novel PKCare activated by PLC activation vía tyrosine kinases and G protein-coupled receptors. Numerous studies established that PKC isoverexpressed in human cancer and its expression correlates withtumor aggressiveness in prostate, lung and breast cancer. However,the role of PKC in thyroid cancer remains poorly studied. We hereaddressed the potential role of PKC in TSHR transduction pathwaysinvolved in cellular proliferation and tumorigenesis. Analysis of PKCexpression in human thyroid cancer cell lines (2 papilar, 1 follicularand 3 anaplastic) revealed high protein and mRNA levels relativeto 2 ?normal? immortalized cell lines. Treatment of thyroid cancercells with TSH induced an increase in cellular proliferation comparedto untreated cells (Ct) (p