Estrogen-induced proliferation in cultured hepatocytes involves cyclin D1, P21CIP1 and P27KIP1
Estrogen-induced proliferation in cultured hepatocytes involves cyclin D1, P21CIP1 and P27KIP1
复制标题
DOI：
10.1007/s10620-006-3173-4
复制
发表时间：
2006-03-01
影响因子：
3.1
通讯作者：
Iolascon, A
中科院分区：
文献类型：
--
作者：
Barone, M;Ladisa, R;Iolascon, A
本研究的目的是确定雌激素诱导的体外肝细胞增殖是否涉及细胞周期调节因子cyclin D1、p21（Cip 1）和p27（Kip 1）。根据需要，在存在17-β-雌二醇（E-2）+/- ICI-182780（一种纯雌激素拮抗剂）和[H-3]-胸苷的情况下培养雄性大鼠肝细胞。在孵育的不同时间（12、24、36和48小时）评价DNA合成以及p21（Cip 1）、p27（Kip 1）和细胞周期蛋白D1 mRNA和蛋白水平。E-2增加的DNA合成与细胞周期蛋白D1和p21（Cip 1）（mRNA和蛋白质）变异相关，而ICI-182780的加入可逆转这些变异。无论是否存在E-2或ICI-182780，p27（Kip 1）蛋白水平均逐渐升高。我们的数据证实，雌激素的刺激作用与其增加细胞周期蛋白D1水平的能力有关。p21（Cip 1）的增加可能与静止状态下肝细胞的再进入有关。p27（Kip 1）蛋白不能抑制肝细胞增殖。
The purpose of this study was to establish if estrogen-induced hepatocyte proliferation in vitro involves the cell cycle regulators cyclin D1, p21(Cip1), and p27(Kip1). Male rat hepatocytes were cultured in presence of 17-beta-estradiol (E-2) +/- ICI-182780, a pure estrogen antagonist, and [H-3]-thymidine, as required. DNA synthesis as well as p21(Cip1), p27(Kip1), and cyclin D1mRNA and protein levels were evaluated at different times (12, 24, 36, and 48 hours) of incubation. E-2-increased DNA synthesis was correlated with cyclin D1 and p21(Cip1) (mRNA and protein) variations that were reversed by the addition of ICI-182780. p27(Kip1) protein levels progressively increased regardless of the presence of E-2 or ICI-182780. Our data confirm that estrogens' stimulatory effect is related to their ability to increase cyclin D1 levels. The increase of p21(Cip1) is probably related to the reentry of hepatocytes in the quiescent state. p27(Kip1) protein is not able to arrest hepatocyte proliferation.