Kitamura K, Mizuno Y, Hatayama I, Sato K, Tamura S, Nagao M, Tsuiki S, Kikuchi K
Section of Biochemistry, Hokkaido University.
Jpn J Cancer Res. 1992 Jan;83(1):66-71. doi: 10.1111/j.1349-7006.1992.tb02353.x.
The mRNA levels of three phosphoseryl/phosphothreonyl protein phosphatases, PP1, PP2A and PP2C, in rat liver have been determined by Northern blot analysis in various stages of rat chemical hepatocarcinogenesis using a Solt-Farber model. Five weeks after administration of diethylnitrosamine, the mRNA levels of PP1 alpha, PP2A and PP2C were elevated 8, 29 and 11 times, respectively, as compared to those of the control livers. However, in primary hepatoma induced according to the Solt-Farber model, the mRNA levels of all three protein phosphatases were dramatically decreased to normal levels or even to much lower levels, whereas the mRNA level of glutathione S-transferase placental form, a tumor marker protein, was greatly elevated as compared with that of the control livers. In a poorly differentiated hepatoma AH13, a line of rat ascites hepatoma, the mRNA level of PP1 alpha was 5.6 times higher than that of the control livers, whereas the mRNA lever of PP2C was almost the same as that of the control livers and the level of PP2A mRNA was distinctly lower than that of the control livers. These data appear to suggest some involvement of protein phosphatases in hepatocarcinogenesis.
利用索尔特 - 法伯模型，通过Northern印迹分析，测定了大鼠化学性肝癌发生不同阶段大鼠肝脏中三种磷酸丝氨酰/磷酸苏氨酰蛋白磷酸酶PP1、PP2A和PP2C的mRNA水平。给予二乙基亚硝胺5周后，与对照肝脏相比，PP1α、PP2A和PP2C的mRNA水平分别升高了8倍、29倍和11倍。然而，在根据索尔特 - 法伯模型诱导的原发性肝癌中，所有三种蛋白磷酸酶的mRNA水平均显著降低至正常水平甚至更低水平，而作为肿瘤标志物蛋白的谷胱甘肽S - 转移酶胎盘型的mRNA水平与对照肝脏相比则大幅升高。在低分化肝癌AH13（一种大鼠腹水肝癌细胞系）中，PP1α的mRNA水平比对照肝脏高5.6倍，而PP2C的mRNA水平与对照肝脏几乎相同，PP2A mRNA水平明显低于对照肝脏。这些数据似乎表明蛋白磷酸酶在肝癌发生过程中存在某种参与作用。
