Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo 189-0002, Japan.
Biochem Biophys Res Commun. 2012 Apr 13;420(3):611-5. doi: 10.1016/j.bbrc.2012.03.046. Epub 2012 Mar 16.
The growth of thyroid cells is tightly regulated by thyroid stimulating hormone (TSH) through the cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathway by potentiating the mitogenic activity of insulin and insulin-like growth factors (IGFs). However, we recently reported that thyroglobulin (Tg), a major product of the thyroid, also induces the growth of thyroid cells cultured in 0.2% serum in the absence of TSH and insulin. In this report, we demonstrate that Tg induced phosphorylation of molecules of the c-Raf/MEK/ERK pathway of the mitogen-activated protein kinase (MAPK). The MEK-1/2 inhibitor PD98059 suppressed Tg-induced phosphorylation of ERK1/2 and reduced bromodeoxyuridine (BrdU) incorporation. Tg also induced expression of the essential transcriptional factors c-Myc, c-Fos and c-Jun and phosphorylation of the retinoblastoma (Rb) protein. The present results, together with the previous report, suggest that Tg utilizes multiple signaling cascades to induce thyroid cell growth independent of TSH/cAMP stimulation.
甲状腺细胞的生长受甲状腺刺激激素 (TSH) 通过环腺苷酸 3'，5'-单磷酸 (cAMP) 信号通路的调节，该通路通过增强胰岛素和胰岛素样生长因子 (IGFs) 的有丝分裂活性。然而，我们最近报道称，甲状腺的主要产物甲状腺球蛋白 (Tg) 也能在没有 TSH 和胰岛素的情况下诱导 0.2%血清培养的甲状腺细胞生长。在本报告中，我们证明 Tg 诱导了丝裂原激活蛋白激酶 (MAPK) 的 c-Raf/MEK/ERK 途径的分子磷酸化。MEK-1/2 抑制剂 PD98059 抑制了 Tg 诱导的 ERK1/2 磷酸化并减少了溴脱氧尿苷 (BrdU) 的掺入。Tg 还诱导了必需转录因子 c-Myc、c-Fos 和 c-Jun 的表达以及视网膜母细胞瘤 (Rb) 蛋白的磷酸化。这些结果与之前的报告一起表明，Tg 利用多种信号级联反应来诱导甲状腺细胞生长，而无需 TSH/cAMP 刺激。
