Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line

被引:105
作者
Xie, L
Law, BK
Aakre, ME
Edgerton, M
Shyr, Y
Bhowmick, NA
Moses, HL
机构
[1] Vanderbilt Univ, Dept Canc Biol, Nashville, TN USA
[2] Vanderbilt Univ, Dept Pathol & Prevent Med, Nashville, TN USA
[3] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA
关键词
adhesion; cDNA microarray; cell cycle control; epithelial; mammary gland;
D O I
10.1186/bcr640
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Transforming growth factor beta (TGF-beta) plays an essential role in a wide array of cellular processes. The most well studied TGF-beta response in normal epithelial cells is growth inhibition. In some cell types, TGF-beta induces an epithelial to mesenchymal transition (EMT). NMuMG is a nontransformed mouse mammary gland epithelial cell line that exhibits both a growth inhibitory response and an EMT response to TGF-beta, rendering NMuMG cells a good model system for studying these TGF-beta effects. Method A National Institutes of Aging mouse 15,000 cDNA microarray was used to profile the gene expression of NMuMG cells treated with TGF-beta1 for 1, 6, or 24 hours. Data analyses were performed using GenePixPro and GeneSpring software. Selected microarray results were verified by northern analyses. Results Of the 15,000 genes examined by microarray, 939 were upregulated or downregulated by TGF-beta. This represents approximately 10% of the genes examined, minus redundancy. Seven genes previously not known to be regulated by TGF-beta at the transcriptional level (Akt and RhoB) or not at all (IQGAP1, mCalpain, actinin alpha3, Ikki, PP2A-PR53), were identified and their regulation by TGF-beta verified by northern blotting. Cell cycle pathway examination demonstrated downregulation of cyclin D-2, c-myc, Id2, p107, E2F5, cyclin A, cyclin B, and cyclin H. Examination of cell adhesion-related genes revealed upregulation of c-Jun, alpha-actinin, actin, myosin light chain, p120cas catenin (Catns), alpha-integrin, integrin beta5, fibronectin, IQGAP1, and mCalpain. Conclusion Using a cDNA microarray to examine TGF-beta-regulated gene expression in NMuMG cells, we have shown regulation of multiple genes that play important roles in cell cycle control and EMT. In addition, we have identified several novel TGF-beta-regulated genes that may mediate previously unknown TGF-beta functions.
引用
收藏
页码:R187 / R198
页数:12
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