Upregulation of Neural Precursor Cell Expressed Developmentally Downregulated 4-1 is Associated with Poor Prognosis and Chemoresistance in Lung Adenocarcinoma  

作　　者：Ying-Hua Song Cai-Qing Zhang Fang-Fang Chen Xiao-Yan Lin 

机构地区：[1]Department of Respiratory Medicine, Shandong Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, China [2]Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China

出　　处：《Chinese Medical Journal》2018年第1期16-24,共9页中华医学杂志（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 81402185）.

摘　　要：Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor developnaent and chemosensitivity of lung adenocarcinoma （ADC）. Methods： We retrospectively investigated the expression and significance ofNEDD4-1, PTEN, and p-Akt proteins in 135 paired A DC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthemaore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- （4,5-dimethylthiazol-2-yl） -5-（3-carboxymethoxyphenyl） -2-（4-sulfophenyl）- 2H-tetrazoliunl method. The ability of migration and invasion ofA549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase （PI3K）/Akt activity, and its downstream target proteins. Results： NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression ofNEDD4-1 in ADC （78.5%, 106/135） was significantly much higher than that in adjacent normal lung tissue （ 13.3%, 29/135, P 〈 0.01）, and it was associated with lymph node metastasis, tumor-node-metastasis （TNM） stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC （60.7% vs. 100.0% in noncancerous specimens, P - 0.007）, and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues （Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor developnaent and chemosensitivity of lung adenocarcinoma （ADC）. Methods： We retrospectively investigated the expression and significance ofNEDD4-1, PTEN, and p-Akt proteins in 135 paired A DC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthemaore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- （4,5-dimethylthiazol-2-yl） -5-（3-carboxymethoxyphenyl） -2-（4-sulfophenyl）- 2H-tetrazoliunl method. The ability of migration and invasion ofA549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase （PI3K）/Akt activity, and its downstream target proteins. Results： NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression ofNEDD4-1 in ADC （78.5%, 106/135） was significantly much higher than that in adjacent normal lung tissue （ 13.3%, 29/135, P 〈 0.01）, and it was associated with lymph node metastasis, tumor-node-metastasis （TNM） stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC （60.7% vs. 100.0% in noncancerous specimens, P - 0.007）, and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues （

关 键 词：CHEMORESISTANCE Lung Adenocarcinoma： NEDD4-1： PTEN 10 PROGNOSIS 

分 类 号：R0[医药卫生]