Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 OC3.5 | DOI: 10.1530/endoabs.32.OC3.5

ECE2013 Oral Communications Thyroid (6 abstracts)

Role of the calcium-calmodulin dependent kinase 2 in medullary thyroid carcinoma

Eleonora Russo 1 , Marcella Salzano 1 , Valentina De Falco 1 , Massimo Santoro 1 , Caterina Mian 2 , Susi Barollo 2 & Mario Vitale 3


1University of Naples Federico II, Naples, Italy; 2University of Padua, Padua, Italy; 3University of Salerno, Baronissi, Salerno, Italy.


Recent studies demonstrated that the calcium/calmodulin dependent kinase 2 (CaMKII) is involved in the regulation of proliferation and survival of epithelial cells, were it phosphorylates RAF-1 and modulates MAPK pathway. A endogenous CaMKII inhibitor (hCaKIINα) is expressed in some cell types. It is down-expressed in colon and in ovarian cancer where it inversely correlates with the disease extension.

Aim of our study is to determine the possible role of CaMKII in the medullary thyroid carcinoma (MTC), to determine whether hCaKIINα is expressed, and whether its level of expression correlates with the clinicopathological features of MTC.

To this purpose, RETC634Y e RETM918T, two RET mutants most frequently found in MTC, were expressed in NIH-3T3 cells and the activation status of CaMKII was determined. Oncogenic RET expression in serum-starved NIH-3T3 mutants induced maximal CaMKII activation. In two MTC cell lines (TT and MZCRC-1 carrying the same RET mutants) CaMKII was activated. Inhibition of CaMKII in these cells induced a reduction of ERK phosphorylation and cell proliferation. Then, the expression of hCaKIINα RNA was determined by real-time PCR in 24 primary MTCs and was correlated with some clinicopathological parameters. Gender and age at diagnosis did not correlate with hCaKIINα RNA expression. Serum calcitonin, (R2=0.032, P=0.017 by Spearman rank correlation), tumor volume (P=0.0094 by ANOVA), lymph node metastasis (P=0.0297 by t-test) and staging (P=0.0043 by ANOVA) were negatively correlated with the hCaMKIINα mRNA expression.

In conclusion, CaMKII is activated by RET mutants and is activated at baseline in MTC cell lines were it mediates the oncogenic pathway leading to cell proliferation. The mRNA expression of its endogenous inhibitor hCaKIINα inversely correlates with the severity of MTC. CaMKII might represent a new target for MTC therapy.

Article tools

My recent searches

No recent searches.