Expression of functional metallothionein isoforms in papillary thyroid cancer.
Metallothionein (MT) isoforms have not been studied in papillary thyroid cancer. We examined how the functional MT1 and MT2 isoforms were expressed in papillary thyroid cancer (KAT5) cells. We demonstrated that KAT5 cells expressed eight functional MT1 and MT2 isoforms induced by cadmium. Elevated calcium and activated ERK1/2 predated MT expression. The inhibition of either calcium or ERK1/2 significantly blocked the isoform expression. The induction of these isoforms accompanied an increased progression of cell cycle from G0/G1 to G2-M. The alternation in cell cycle disappeared when the expression of MT isoforms was blocked by calcium inhibitor or ERK1/2 inhibitor. Collectively, KAT5 cells express eight functional MT1 and MT2 isoforms in a pathway controlled by calcium and ERK1/2. The elevation of the MT isoforms contributes to the decreased G0/G1 but increased G2-M phase. These results reveal a novel pathway for the expression of the functional MT in papillary thyroid cancer.
Department of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Zhi-Min
ZM
Liu
C Andrew van
CA
Hasselt
Fang-Zhou
FZ
Song
Alexander C
AC
Vlantis
M George
MG
Cherian
James
J
Koropatnick
George G
GG
Chen
D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008668:Metallothionein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008668:Metallothionein