WT1 Promotes Invasion of NSCLC via Suppression of CDH1

Autor: Chen Wu, Yijiang Chen, Jing Qian, Yongqian Shu, Changping Wu, Weiyou Zhu, Shaohua He
Rok vydání: 2013
Předmět:
Male
Lung Neoplasms
Apoptosis
urologic and male genital diseases
CDH1
Metastasis
Immunoenzyme Techniques
Small hairpin RNA
Cell Movement
Carcinoma
Non-Small-Cell Lung

Neoplasm Metastasis
RNA
Small Interfering

Promoter Regions
Genetic

Aged
80 and over

Gene knockdown
Reverse Transcriptase Polymerase Chain Reaction
Middle Aged
Cadherins
Prognosis
female genital diseases and pregnancy complications
Gene Expression Regulation
Neoplastic

Real-time polymerase chain reaction
Oncology
Carcinoma
Squamous Cell

Female
Pulmonary and Respiratory Medicine
congenital
hereditary
and neonatal diseases and abnormalities

Blotting
Western

Adenocarcinoma
Biology
Real-Time Polymerase Chain Reaction
Antigens
CD

medicine
Humans
Neoplasm Invasiveness
RNA
Messenger

WT1 Proteins
Lung cancer
Aged
Cell Proliferation
Neoplasm Staging
Wound Healing
Oncogene
urogenital system
Cell growth
medicine.disease
Molecular biology
respiratory tract diseases
Case-Control Studies
Cancer research
biology.protein
Follow-Up Studies
Zdroj: Journal of Thoracic Oncology. 8:1163-1169
ISSN: 1556-0864
Popis: Introduction: The Wilms' tumor gene ( WT1 ) has been identified as an oncogene in many malignant diseases, and aberrant WT1 expression has been linked to development, progression, and prognosis of non–small-cell lung cancer (NSCLC). We sought to investigate the underlying mechanism of WT1 and metastasis in NSCLC. Methods: Real-time polymerase chain reaction was applied to detect WT1 and CDH1 mRNA in 159 NSCLC samples and corresponding adjacent tissues. Stable clones with overexpression and knockdown of WT1 were generated with plasmid and shRNA via lentivirus technology in H1568 and H1650 NSCLC cell lines. Wound-healing assay, transwell assays, and polymerase chain reaction array were carried out for invasion evaluation. Dual luciferase reporter assay was performed to validate the effect of WT1 on CDH1 . Results: The level of the WT1 mRNA was negatively correlated with that of E-cadherin ( CDH1 ) and associated with pathological stage, metastasis, and survival rate of 159 NSCLC patients. A series of genes were regulated by WT1 , and WT1 could suppress CDH1 transcription via direct binding to its promoter and may enhance the invasive ability of H1568 and H1650 NSCLC cell lines. Conclusions: WT1 expression was correlated with clinical stage, metastasis, and survival rate in 159 NSCLC patients. Via direct binding to the promoter, WT1 could suppress CDH1 and promote NSCLC invasion.
Databáze: OpenAIRE