Identification of genes regulated by Wnt/β-catenin pathway and involved in apoptosis via microarray analysis

• Main Authors: Chen Quan, Wang Shengqi, Bai Jinfeng, Quan Lanping, Yang Shangbin, Zhang Wei, Yin Yanbing, Zhu Hongxia, Sun Daochun, Wang Yihua, Huang Moli, Li Songgang, Xu Ningzhi
• Format: Article
• Language: English
• Published: BMC 2006-09-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/6/221

<p>Abstract</p> <p>Background</p> <p>Wnt/β-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/β-catenin pathway modification of the cellular apoptosis.</p> <p>Methods</p> <p>To identify potential genes regulated by Wnt/β-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of β-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR.</p> <p>Results</p> <p>Stably integrated inducible RNAi vector could effectively suppress β-catenin expression and the transcriptional activity of β-catenin/TCF. Meanwhile, depletion of β-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-κB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of β-catenin.</p> <p>Conclusion</p> <p>Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/β-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified β-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth.</p>