Rezzonico R, Loubat A, Lallemand D, Pfarr C M, Far D F, Proudfoot A, Rossi B, Ponzio G
INSERM U364, Faculté de Médecine, Nice, France.
Oncogene. 1995 Sep 21;11(6):1069-78.
Interleukin-6 (IL-6) is a proinflammatory cytokine which also acts as a growth factor for some murine hybridomas (7TD1) or human myelomas (U266). We demonstrate that elevation of cAMP cellular content inhibits IL-6-stimulated cell growth, by blocking cells mainly in G1 phase. This inhibition is associated with increased expression of the Fos family protein Fra-2. Treatment of cells with 8Br-cAMP results in increased DNA-binding activity of two distinct AP-1 complexes; JunD/Fra-2 and JunB/Fra-2, and also in elevated AP-1 transactivation. When 8Br-cAMP is withdrawn from the medium, cells enter S phase and Fra-2 protein levels and AP-1 DNA-binding activity decrease to their basal value indicating that a temporally correlation exists between the 8Br-cAMP-mediated induction of JunD/Fra-2 AP-1 complex and the 7TD1 and U266 cell growth inhibition.
白细胞介素-6（IL-6）是一种促炎细胞因子，它还可作为某些鼠杂交瘤（7TD1）或人骨髓瘤（U266）的生长因子。我们证明，细胞内cAMP含量的升高通过将细胞主要阻滞在G1期来抑制IL-6刺激的细胞生长。这种抑制作用与Fos家族蛋白Fra-2的表达增加有关。用8-溴-cAMP处理细胞会导致两种不同的AP-1复合物（JunD/Fra-2和JunB/Fra-2）的DNA结合活性增加，同时AP-1转录激活也增强。当从培养基中去除8-溴-cAMP时，细胞进入S期，Fra-2蛋白水平和AP-1 DNA结合活性降至基础值，这表明8-溴-cAMP介导的JunD/Fra-2 AP-1复合物诱导与7TD1和U266细胞生长抑制之间存在时间相关性。
