PKC alpha activation by TSH plays a key role in thyroid cancer cell proliferation

ROSEMBLIT C; DIAZ FLAQUE MC; BARREIRO ARCOS ML; CAYROL MF; PERONA M; JUVENAL GJ; CREMASCHI GA

Congreso; XVII Latin American Thyroid Society Congress.; 2019

Latin American Thyroid Society

Introduction: Thyroid cancer (TC) incidence has increased significantly within last decades. Thyroid stimulating hormone (TSH) controls thyroid function by binding to TSH G-protein-coupled receptor (TSHR). PKC, a serine/threonine protein kinase, has been widely implicated in malignant transformation, cell survival, motility and invasion. Classical and novel PKC are activated by PLCactivation via tyrosine kinases and G-protein-coupled receptors. Numerous studies established that PKC is overexpressed in cancer and its expression correlates with aggressiveness. However, the role of PKC in TC remains poorly studied. Objectives: To study the role of PKCα in TSH-induced proliferation in TC cells. Methods: TPC-1 papillary TC cell viability was evaluated by cell titter blue assay. Protein modulation was measured by qPCR, western blot and flow cytometry. siRNA transfection was used to knock down PKCα expression. Results: PKC expression in human TC cell lines revealed high protein and mRNA levels relative to normal cell lines. Treatment of TC cells with TSH increased cellular proliferation compared to untreated cells (p < 0.05). Treatment with PKC inhibitors Staurosporine (St) and GF109203X (GF) resulted in a significant inhibition of TSH-mediated proliferation compared to control (p < 0.05). Also, treatment with St and GF diminished AKT and Erk activation in TSH-stimulated cells. Finally, PKCα-depleted cells reduced significantly TSH-induced proliferation. Our results show that PKCα is implicated in AKT and Erk phosphorylation. Conclusion: Our findings establish a potential role for PKC in the control of hormone-induced proliferation that can be explored as treatment to effectively eliminate TC cells. Conflict of interest: None declared.