C66
Calcium and ERK1/2 play a critical role in the expression of functional metallothionein isoforms in papillary thyroid cancer cells
George G Chen, Zhimin Liu, Alexander Alexander C Vlantis, C Andrew C Andrew van Hasselt
The Chinese University of Hong Kong, Shatin, NT, Hong Kong
Background
Metallothioneins (MT) participate in the development, progression and prognosis of cancers. The mechanism leading to MT expression is unknown and the functional MT1 and MT2 isoforms have not been studied in human papillary thyroid cancer.
Method
This study examined the mechanism responsible for the expression of the functional MT1 and MT2 isoforms using cell cultures, real-time RT-PCR, Western blot and cell cycle analysis inhuman papillary thyroid cancer (KAT5) cells.
Results
Using real-time RT-PCR, we demonstrated that KAT5 cells expressed 8 functional MT1 and MT2 isoforms induced by cadmium. The MT inducer cadmium elevated calcium and activated ERK1/2 before the induction of MT isoforms. Furthermore, the blockage of either calcium or ERK1/2 completely inhibited or significantly blocked the cadmium-induced MT1 and MT2 isoform expression, suggesting that both calcium and ERK1/2 play a critical role in the induction of the functional MT isoforms. The induction of the functional MT isoforms accompanied an increased progression of cell cycle from G0/G1 to G2-M. The alternation in cell cycle disappeared when the induction of MT isoforms was blocked by either calcium or ERK1/2 inhibitors.
Conclusion
Human papillary thyroid cancer cells can express 8 functional MT1 and MT2 isoforms in a pathway controlled by calcium and ERK1/2. The elevation of the MT isoforms may contribute to the decrease of the cells in G0/G1 phase but increase in G2-M phase. These results formulate a novel pathway for the expression of the functional MT1 and MT2 in the papillary thyroid cancer.
