雌激素诱导的培养肝细胞增殖涉及细胞周期蛋白D1、p21（Cip1）和p27（Kip1）。

Estrogen-induced proliferation in cultured hepatocytes involves cyclin D1, p21(Cip1) and p27(Kip1).

作者信息

Barone M, Ladisa R, Di Leo A, Spano D, Francioso D, Aglio V, Amoruso A, Francavilla A, Iolascon A

机构信息

Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.

出版信息

Dig Dis Sci. 2006 Mar;51(3):580-6. doi: 10.1007/s10620-006-3173-4.

DOI:10.1007/s10620-006-3173-4

PMID:16614970

Abstract

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 (E2) +/- ICI-182780, a pure estrogen antagonist, and [3H]-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. E2-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 E2 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.

摘要

本研究的目的是确定雌激素在体外诱导的肝细胞增殖是否涉及细胞周期调节因子细胞周期蛋白D1、p21（Cip1）和p27（Kip1）。根据需要，将雄性大鼠肝细胞在17-β-雌二醇（E2）±ICI-182780（一种纯雌激素拮抗剂）和[3H]-胸腺嘧啶存在的情况下进行培养。在孵育的不同时间点（12、24、36和48小时）评估DNA合成以及p21（Cip1）、p27（Kip1）、细胞周期蛋白D1的mRNA和蛋白质水平。E2诱导的DNA合成增加与细胞周期蛋白D1和p21（Cip1）（mRNA和蛋白质）的变化相关，添加ICI-182780可逆转这些变化。无论是否存在E2或ICI-182780，p27（Kip1）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（Cip1）的增加可能与肝细胞重新进入静止状态有关。p27（Kip1）蛋白无法阻止肝细胞增殖。