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

Lu Xie, Brian K. Law, Mary E. Aakre, Mary Edgerton, Yu Shyr, Neil A. Bhowmick, Harold L. Moses

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Background: Transforming growth factor beta (TGF-β) plays an essential role in a wide array of cellular processes. The most well studied TGF-β response in normal epithelial cells is growth inhibition. In some cell types, TGF-β 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-β, rendering NMuMG cells a good model system for studying these TGF-β 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-β1 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-β. This represents approximately 10% of the genes examined, minus redundancy. Seven genes previously not known to be regulated by TGF-β at the transcriptional level (Akt and RhoB) or not at all (IQGAP1, mCalpain, actinin α3, Ikki, PP2A-PR53), were identified and their regulation by TGF-β verified by northern blotting. Cell cycle pathway examination demonstrated downregulation of cyclin D2, c-myc, Id2, p107, E2F5, cyclin A, cyclin B, and cyclin H. Examination of cell adhesion-related genes revealed upregulation of c-Jun, α-actinin, actin, myosin light chain, p120cas catenin (Catns), α-integrin, integrin β5, fibronectin, IQGAP1, and mCalpain. Conclusion: Using a cDNA microarray to examine TGF-β-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-β-regulated genes that may mediate previously unknown TGF-β functions.

Original languageEnglish
Article numberR187
JournalBreast Cancer Research
Volume5
Issue number6
DOIs
Publication statusPublished - 2003 Dec 1

Fingerprint

Human Mammary Glands
Transforming Growth Factor beta
Epithelial Cells
Gene Expression
Cell Line
Epithelial-Mesenchymal Transition
Genes
Actinin
Oligonucleotide Array Sequence Analysis
Integrins
Cyclin H
Down-Regulation
Cyclin D2
Cyclin B
Cyclin A
Catenins
Myosin Light Chains
Growth
Cell Cycle Checkpoints
Transcriptome

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Xie, Lu ; Law, Brian K. ; Aakre, Mary E. ; Edgerton, Mary ; Shyr, Yu ; Bhowmick, Neil A. ; Moses, Harold L. / Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line. In: Breast Cancer Research. 2003 ; Vol. 5, No. 6.
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abstract = "Background: Transforming growth factor beta (TGF-β) plays an essential role in a wide array of cellular processes. The most well studied TGF-β response in normal epithelial cells is growth inhibition. In some cell types, TGF-β 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-β, rendering NMuMG cells a good model system for studying these TGF-β 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-β1 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-β. This represents approximately 10{\%} of the genes examined, minus redundancy. Seven genes previously not known to be regulated by TGF-β at the transcriptional level (Akt and RhoB) or not at all (IQGAP1, mCalpain, actinin α3, Ikki, PP2A-PR53), were identified and their regulation by TGF-β verified by northern blotting. Cell cycle pathway examination demonstrated downregulation of cyclin D2, c-myc, Id2, p107, E2F5, cyclin A, cyclin B, and cyclin H. Examination of cell adhesion-related genes revealed upregulation of c-Jun, α-actinin, actin, myosin light chain, p120cas catenin (Catns), α-integrin, integrin β5, fibronectin, IQGAP1, and mCalpain. Conclusion: Using a cDNA microarray to examine TGF-β-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-β-regulated genes that may mediate previously unknown TGF-β functions.",
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Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line. / Xie, Lu; Law, Brian K.; Aakre, Mary E.; Edgerton, Mary; Shyr, Yu; Bhowmick, Neil A.; Moses, Harold L.

In: Breast Cancer Research, Vol. 5, No. 6, R187, 01.12.2003.

Research output: Contribution to journalArticle

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T1 - Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line

AU - Xie, Lu

AU - Law, Brian K.

AU - Aakre, Mary E.

AU - Edgerton, Mary

AU - Shyr, Yu

AU - Bhowmick, Neil A.

AU - Moses, Harold L.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Background: Transforming growth factor beta (TGF-β) plays an essential role in a wide array of cellular processes. The most well studied TGF-β response in normal epithelial cells is growth inhibition. In some cell types, TGF-β 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-β, rendering NMuMG cells a good model system for studying these TGF-β 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-β1 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-β. This represents approximately 10% of the genes examined, minus redundancy. Seven genes previously not known to be regulated by TGF-β at the transcriptional level (Akt and RhoB) or not at all (IQGAP1, mCalpain, actinin α3, Ikki, PP2A-PR53), were identified and their regulation by TGF-β verified by northern blotting. Cell cycle pathway examination demonstrated downregulation of cyclin D2, c-myc, Id2, p107, E2F5, cyclin A, cyclin B, and cyclin H. Examination of cell adhesion-related genes revealed upregulation of c-Jun, α-actinin, actin, myosin light chain, p120cas catenin (Catns), α-integrin, integrin β5, fibronectin, IQGAP1, and mCalpain. Conclusion: Using a cDNA microarray to examine TGF-β-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-β-regulated genes that may mediate previously unknown TGF-β functions.

AB - Background: Transforming growth factor beta (TGF-β) plays an essential role in a wide array of cellular processes. The most well studied TGF-β response in normal epithelial cells is growth inhibition. In some cell types, TGF-β 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-β, rendering NMuMG cells a good model system for studying these TGF-β 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-β1 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-β. This represents approximately 10% of the genes examined, minus redundancy. Seven genes previously not known to be regulated by TGF-β at the transcriptional level (Akt and RhoB) or not at all (IQGAP1, mCalpain, actinin α3, Ikki, PP2A-PR53), were identified and their regulation by TGF-β verified by northern blotting. Cell cycle pathway examination demonstrated downregulation of cyclin D2, c-myc, Id2, p107, E2F5, cyclin A, cyclin B, and cyclin H. Examination of cell adhesion-related genes revealed upregulation of c-Jun, α-actinin, actin, myosin light chain, p120cas catenin (Catns), α-integrin, integrin β5, fibronectin, IQGAP1, and mCalpain. Conclusion: Using a cDNA microarray to examine TGF-β-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-β-regulated genes that may mediate previously unknown TGF-β functions.

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