Shimizu E, Zhao M, Shinohara A, Namikawa O, Ogura T, Masuda N, Takada M, Fukuoka M, Sone S
Third Department of Internal Medicine, Tokushima University School of Medicine, Japan.
J Cancer Res Clin Oncol. 1997;123(10):533-8. doi: 10.1007/s004320050101.
Cell-cycle-dependent phosphorylation of the tumor-suppressor protein product of the retinoblastoma gene (RB) is mediated by a family of cyclin-dependent kinases and cyclins. We examined the expressions of RB protein and cyclin A protein in 13 small-cell lung cancer (SCLC) lines and 14 non-small-cell lung cancer (NSCLC) lines by immunoblotting. RB protein was not present or was of a mutant type in 77% of the SCLC lines (10/13) but was present in all the NSCLC lines. Cyclin A was expressed in 38% of the SCLC lines (5/13) and in 86% of the NSCLC lines (12/14). A positive correlation (P = 0.0034) between expression of cyclin A and wild-type RB protein was found by Fisher's exact probability test. Densitometric analysis of the expression of RB protein in RB(+) lung cancer lines showed that the phosphorylated form was predominant in 2/3 of the SCLC and 8/14 of the NSCLC lines. The positive correlation between the expressions of RB protein and cyclin A suggests that RB protein in most RB(+) lung cancer cell lines is a target of cyclin-A-dependent kinase and that the tumor-suppressor function may be inactivated by phosphorylation.
视网膜母细胞瘤基因（RB）的肿瘤抑制蛋白产物的细胞周期依赖性磷酸化由细胞周期蛋白依赖性激酶和细胞周期蛋白家族介导。我们通过免疫印迹法检测了13个小细胞肺癌（SCLC）细胞系和14个非小细胞肺癌（NSCLC）细胞系中RB蛋白和细胞周期蛋白A蛋白的表达。77%的SCLC细胞系（10/13）中不存在RB蛋白或其为突变型，但所有NSCLC细胞系中均存在RB蛋白。细胞周期蛋白A在38%的SCLC细胞系（5/13）和86%的NSCLC细胞系（12/14）中表达。通过Fisher精确概率检验发现细胞周期蛋白A的表达与野生型RB蛋白之间存在正相关（P = 0.0034）。对RB（+）肺癌细胞系中RB蛋白表达的光密度分析表明，磷酸化形式在2/3的SCLC细胞系和8/14的NSCLC细胞系中占主导。RB蛋白和细胞周期蛋白A表达之间的正相关表明，大多数RB（+）肺癌细胞系中的RB蛋白是细胞周期蛋白A依赖性激酶的作用靶点，并且肿瘤抑制功能可能因磷酸化而失活。
