Yu L, Kubota H, Imai K, Yamaguchi M, Nagasue N
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Liver. 1997 Feb;17(1):35-40. doi: 10.1111/j.1600-0676.1997.tb00776.x.
Heterogeneity in the growth response to androgen and androgen receptor (AR) status in an AR-positive human hepatocellular carcinoma (HCC) line, KYN-1, was investigated in the present study. Seven sublines were obtained from KYN-1 by the limited dilution method. Four of them had no detectable amounts of AR and did not show any growth response to dihydrotestosterone (DHT) at the concentration up to 1000 nM, while the other three had varying amounts of both cytosolic and nucleosolic AR that were 5- to 7-fold higher than that of the parent cell. In the parent cell, the addition of DHT caused a modest but significant increase in the cell number (21%) in a 14-day culture. Such effect was increased by 2- to 7-fold in two AR-positive sublines. In addition, the sensitivity of the response in these two sublines was increased by up to 24-fold. The one remaining AR-positive subline did not show any growth response to DHT, although the behavior of its AR in sucrose gradient ultracentrifugation and Western blotting was the same as that of the other two sublines. These data clearly show that sublines derived from an established human HCC line have a broad heterogeneity in the growth response of HCC to androgen as well as in AR status and could be classified into three groups on the basis of the growth responsiveness to androgen and the AR expression.
本研究调查了AR阳性人肝癌（HCC）细胞系KYN-1对雄激素的生长反应及雄激素受体（AR）状态的异质性。通过有限稀释法从KYN-1获得了7个子系。其中4个检测不到AR，在高达1000 nM的浓度下对双氢睾酮（DHT）无生长反应，而另外3个细胞溶质和核溶质AR含量不同，比亲代细胞高5至7倍。在亲代细胞中，添加DHT在14天培养中使细胞数量适度但显著增加（21%）。在两个AR阳性子系中，这种效应增加了2至7倍。此外，这两个子系反应的敏感性提高了24倍。剩下的一个AR阳性子系对DHT无生长反应，尽管其AR在蔗糖梯度超速离心和蛋白质免疫印迹中的行为与其他两个子系相同。这些数据清楚地表明，源自已建立的人肝癌细胞系的子系在肝癌对雄激素的生长反应以及AR状态方面具有广泛的异质性，并且可以根据对雄激素的生长反应性和AR表达分为三组。
