Cytoplasmic Mislocalization of p27 kipl Protein Resulted from Akt Correlates with Poor Prognosis in Lung Adenocarcinoma

作     者：Yah Xie~(1a▲) Xin Wang~(1b▲) Huiling Yang~(1a※) Ruiying Zhao~2 Xiang Tao~(1a) Huizhong Zhang~(1b) Chunhong Yan~(1a) Yubiao Guo~(1c) Chun-Hui Su~2 Changju Qu~(1a) Mong-Hong Lee~2 1.1a.Department of Pathophysiology,the School of Preclincal Medicine,1b.Department of Thoracic Oncology and Pathology,Cancer Center,1c.Respiratory Division,The first Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,P.R.China 2.Department of Molecular and Cellular Oncology,University of Texas,MD Anderson Cancer Center,Houston,TX,USA 

会议名称：《2008年中国病理生理学会第十一届肿瘤和第十二届免疫专...》

会议日期：2008年

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Major Program (No.2004A30801006) International Cooperation Program (No.2004B50301003) the Guangdong Social Development Project of Science and Technology,International Cooperation Program of Science and Technology Fundation of Guangzhou (No.2004J1-I0041) 

关 键 词：Akt p27Kip 1 lung adenocarcinoma immunohistochemistry Live-cell imaging 

摘      要：正To cell cycle,Akt is a positive regulator,while nuclear p27Kipl is a negative *** was shown that Akt or P-Akt was related with p27Kipl in cancer cell *** non-small cell lung cancer （NSCLC）,Akt was overexpressed,which was associated with the poor *** primary breast cancer,we found the P-S473Akt was upregulated,tumor suppressor 14-3-3σwas downregulated,and the down- regulated 14-3-3σand upregulated P-S473Akt were strongly inverse *** acute myelogenous leukemia,Akt regulated phosphorylation at Thr157 of ***, we detected the localization and expression of p27Kip1 and Akt protein,and evaluated the relationship of Akt and p27Kip1 and their impact on prognosis,stage or tumor grade in human lung adenocarcinoma *** observed that Akt （88%,52 of 59） and P-S473Akt （32%,21of 59） in tumor tissue were overexpressed compared with that in nornal tissue （23%,6 of 26 and 3.85%,1 of 26 respectively） （P0.01）.While the expression of nuclear p27Kip1（Np27 Kip1） （37%,18 of 59） in tumor tissue was predominantly lower than that in normal tissues （21 of 26,81%） （P0.01）;the expression of cytoplasmic p27Kipl（Cp27 Kipl） （81%,48 of 59） in tumor tissue was predominantly higher than that（42.31%,11 of 26） in normal tissues （P0.01）.In the tumor tissues the statistical analysis revealed that Akt was positively associated with P-S473Akt （R=0.365, P0.05）,Np27Kip 1 correlated inversely with that of Cp27Kipl （R=-0.312,P0.05）,P-S473Akt was negatively related to Cp27Kipl （R=-0.347,P0.01）.P-S473Akt and Akt was positively associated with Cp27Kipl level （R=0.308 and 0.319,P0.05）.Moreover,the expressions of P-S473Akt and Np27Kip1 had significant correlations with many clinicopathologic variables （P0.01 or 0.05） of human lung adenocarcinoma *** analysis identified P-S473Akt or N p27Kipl protein as a significant independent prognostic factor （P=0.04 and 0.014,respectively）.Live-cell imaging and western blot analyses of the cell