Growth suppression of thyroid cancer cells by adenylcyclase activator.
Thyroid stimulating hormone (TSH) is known to increase intracytoplasmic cyclic adenosine monophosphate (cAMP) and to regulate the growth of normal follicular cells. The aim of this study was to explore the role of the cAMP-mediated signaling pathway stimulated by TSH as a cell growth modulator in human thyroid cancer cells. One papillary thyroid cancer cell line, K1 cells and two anaplastic thyroid cancer cell lines, TTA1 and TTA2 cells were treated with forskolin, which directly activates adenyl cyclase to raise the level of intracellular cAMP. Forskolin suppressed thyroid cancer cell proliferations, especially in K1 cells, in a dose-dependent manner and induced growth arrest at the G0/G1 phase of the cell cycle. We also examined the expression of mitogen activated protein kinase (MAPK) after the forskolin treatment. Forskolin reduced the activation of growth factor induced MAPK activity. In conclusion, we demonstrated that forskolin was involved in G1 arrest and MAPK activation in K1 thyroid cancer cells. Our study suggests that the TSH signal mediated by cAMP acts as a negative regulator in thyroid cancer cells, unlike that in normal follicular cells.
Yano
Yukiko
Y
Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8577, Japan.
Kamma
Hiroshi
H
Matsumoto
Hirofumi
H
Fujiwara
Masachika
M
Bando
Hiroko
H
Hara
Hisato
H
Yashiro
Tohru
T
Ueno
Ei
E
Ito
Koichi
K
Uchida
Kazuhiko
K
D000262:Adenylyl Cyclases / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D011989:Receptors, Thyrotropin; D005576:Colforsin; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D020929:Mitogen-Activated Protein Kinase Kinases; D000262:Adenylyl Cyclases