Elevated expression of CDK4 in lung cancer

Wu Aibing, Wu Bin, Guo Jinsong, Luo Weiren, Wu Dong, Yang Huiling, Zhen Yan, Yu Xiaoli, Wang Hao, Zhou Ying, Zhen Liu, Fang Weiyi, Yang Zhixiong

Description

Background The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 ( CDK4 ) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of CDK4 -mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer. Methods Using immunohistochemistry analysis, we analyzed CDK4 protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear CDK4 immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of CDK4 and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression. Results The expression level of CDK4 protein was significantly increased in lung cancer tissues compared to normal tissues ( P < 0.001). In addition, high levels of CDK4 protein were positively correlated with the status of pathology classification ( P = 0.047), lymph node metastasis ( P = 0.007), and clinical stage ( P = 0.004) of lung cancer patients. Patients with higher CDK4 expression had a markedly shorter overall survival time than patients with low CDK4 expression. Multivariate analysis suggested the level of CDK4 expression was an independent prognostic indicator ( P < 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of CDK4 in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing CDK4 expression also significantly elevated the expression of cell cycle regulator p21 Conclusion Overexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Wuet al.Journal of Translational Medicine2011,9:38 http://www.translationalmedicine.com/content/9/1/38

R E S E A R C H

Open Access

Elevated expression of CDK4 in lung cancer 1†2†6†1 2 4 1 1 1 Aibing Wu , Bin Wu , Jinsong Guo , Weiren Luo , Dong Wu , Huiling Yang , Yan Zhen , Xiaoli Yu , Hao Wang , 1 3* 1* 5* Ying Zhou , Zhen Liu , Weiyi Fang and Zhixiong Yang

Background:The aim of the present study was to analyze the expression of Cyclindependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement ofCDK4mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer. Methods:Using immunohistochemistry analysis, we analyzedCDK4protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclearCDK4immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level ofCDK4and clinical features was analyzed. Furthermore, we used lentiviralmediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression. Results:The expression level ofCDK4protein was significantly increased in lung cancer tissues compared to normal tissues (P< 0.001). In addition, high levels ofCDK4protein were positively correlated with the status of pathology classification (P= 0.047), lymph node metastasis (P= 0.007), and clinical stage (P= 0.004) of lung cancer patients. Patients with higherCDK4expression had a markedly shorter overall survival time than patients with low CDK4expression. Multivariate analysis suggested the level ofCDK4expression was an independent prognostic indicator (P< 0.001) for the survival of patients with lung cancer. Use of lentiviralmediated shRNA to inhibit the expression ofCDK4in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressingCDK4expression also significantly elevated the expression of cell cycle regulatorp21 Conclusion:OverexpressedCDK4is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression ofp21in lung cancer

Background Lung cancer is the world’s most prevalent cancer accord ing to the World Health Organization, with 1.2 million new cases every year. Nearly all lung cancers arise due to smoking and men are more frequently diagnosed than women. However, a rise in female smoking worldwide has started reversing the trend. In China, about 300,000 lung cancer patients (23/ 100,000) are diagnosed each year [1]. Unfortunately, most

* Correspondence: [e-mail]; [e-mail]; [e-mail] †Contributed equally 1 Cancer Research Institute of Southern Medical University, 510515, Guangzhou, PR China 3 Department of Pathology, Medical College of Guangzhou, 510450, Guangzhou, PR China Full list of author information is available at the end of the article

lung cancer patients tend to present with an advanced stage of disease due to its deep location within the lungs and lack of symptoms during early stages. This may con tribute to the overall poor prognosis of most lung cancer patients. Therefore, it is of great interest to identify factors which provide early diagnosis, more accurate prognosis prediction, and allow development of novel therapeutic strategies. Genetic abnormalities found in lung cancer typically affect two general classes of genes: oncogenes and tumor suppressors. Cancerpromoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, or loss of respect for normal tissue boundaries.CDK4is part of the cyclindependent kinase family. The protein encoded by this gene is a member of

© 2011 Wu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.