Cyclic AMP-mediated growth suppression and MAPK phosphorylation in XXXX cells.

@entity268 @entity1377 @entity8958 @entity3557 @entity9704 @entity10242 @entity15293 @entity817
The main regulating systems of thyroid growth are the mitogen-activated protein kinase (MAPK) signaling pathway and the @entity268 signaling pathway. @entity3557 frequently involves mutations in @entity817 or @entity8958 /PTC without overlap, which are expected to constitutively activate MAPK signaling. On the other hand, it has been reported that @entity268 signaling acts in an inhibitory manner on the proliferation of @entity1377 cell lines, although the @entity268 pathway physiologically promotes the proliferation of normal follicular cells as well as hormonogenesis. The effect of @entity268 on proliferation is attributed to crosstalk with MAPK signaling. However, this phenomenon has not been clearly established in @entity1377 with @entity817 or @entity8958 /PTC mutations. In order to elucidate whether activated @entity268 signaling inhibits cell proliferation and affects MAPK signaling in @entity1377 , we performed in vitro experiments using two representative cell lines, K1 and @entity15293 , which have a @entity817 and an @entity8958 /PTC mutation, respectively. Elevated @entity268 caused by an adenylate cyclase activator suppressed the proliferation of both K1 and @entity15293 cells. Examining the crosstalk between @entity268 and MAPK signaling, K1 and @entity15293 cells showed opposite responses to @entity268 activation. These responses were blocked by an inhibitor of the @entity268 -dependent protein kinase (PKA). In K1 cells, @entity817 might predominate over @entity10242 , and the elevated @entity268 is thought to promote MAPK phosphorylation through the PKA-mediated activation of @entity9704 . On the other hand, in @entity15293 cells @entity10242 might predominate and could be inhibited by activated @entity9704 , resulting in the suppression of MAPK phosphorylation. In conclusion, the proliferation of both @entity1377 cell types was significantly suppressed by @entity268 signaling, regardless of whether MAPK signaling was activated or inactivated by the PKA-mediated @entity268 signaling pathway. There could, however, be other mechanisms by which @entity268 signaling inhibits the growth of @entity1377 cells.
