Kalinichenko Svetlana V, Kopantzev Eugene P, Korobko Elena V, Palgova Irina V, Zavalishina Larisa E, Bateva Maria V, Petrov Andrey N, Frank Georgii A, Sverdlov Eugene D, Korobko Igor V
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Lung Cancer. 2008 Nov;62(2):173-80. doi: 10.1016/j.lungcan.2008.03.022. Epub 2008 May 23.
Pdcd4 (programmed cell death 4) gene is tumor suppressor which expression is frequently down-regulated in tumors, which is considered as a diagnostic and prognostic marker as well as promising target for anti-cancer therapy. Pdcd4 protein is a target for post-translational regulation by phosphorylation marking Pdcd4 for degradation. We questioned if Pdcd4 mRNA decline in human lung tumors is accompanied by proportional depletion of Pdcd4 protein. We found that Pdcd4 protein-to-mRNA ratio varies greatly in human lung cancer cell lines. In squamous cell carcinoma samples where Pdcd4 mRNA suppression was found to be a typical event, Pdcd4 protein level frequently remained unchanged or even up-regulated. Our studies demonstrate that at least in squamous cell carcinoma, alterations in Pdcd4 mRNA and protein levels are not directly linked, and this fact should be taken into consideration when developing Pdcd4-based anti-cancer therapeutic approaches.
Pdcd4（程序性细胞死亡4）基因是一种肿瘤抑制基因，其表达在肿瘤中经常下调，被视为诊断和预后标志物以及抗癌治疗的潜在靶点。Pdcd4蛋白是翻译后磷酸化调控的靶点，磷酸化标记Pdcd4以便降解。我们质疑人类肺癌中Pdcd4 mRNA的下降是否伴随着Pdcd4蛋白的相应减少。我们发现Pdcd4蛋白与mRNA的比例在人类肺癌细胞系中差异很大。在发现Pdcd4 mRNA抑制是典型事件的鳞状细胞癌样本中，Pdcd4蛋白水平经常保持不变甚至上调。我们的研究表明，至少在鳞状细胞癌中，Pdcd4 mRNA和蛋白水平的改变没有直接联系，在开发基于Pdcd4的抗癌治疗方法时应考虑这一事实。
