Runx2, a target gene for activating transcription factor-3 in human breast cancer cells

M. Gokulnath, Nicola Partridge, N. Selvamurugan

Research output: Contribution to journalArticle

Abstract

Activating transcription factor (ATF-3) is a stress response gene and is induced by transforming growth factor beta 1 (TGF-β1) in breast cancer cells. In this study, we dissected the functional role of ATF-3 gene in vitro by knocking down its expression stably in human bone metastatic breast cancer cells (MDA-MB231). Knockdown of ATF-3 expression in these cells decreased cell number, altered cell cycle phase transition, and decreased mRNA expression of cell cycle genes. Knockdown of ATF-3 expression in MDA-MB231 cells also decreased cell migration, and the expression levels of invasive and metastatic genes such as MMP-13 and Runx2 were found to be decreased in these cells. Most importantly, ATF-3 was associated with Runx2 promoter in MDA-MB231 cells and knockdown of ATF-3 expression decreased its association with Runx2 promoter. Hence, our results suggested that ATF-3 plays a role in proliferation and invasion of bone metastatic breast cancer cells in vitro and we identified for the first time that Runx2 is a target gene of ATF-3 in MDA-MB231 cell line.

Original languageEnglish (US)
Pages (from-to)1923-1931
Number of pages9
JournalTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Volume36
Issue number3
DOIs
StatePublished - Mar 1 2015

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Breast Neoplasms
Genes
Activating Transcription Factor 3
Bone and Bones
cdc Genes
Phase Transition
human ATF3 protein
Matrix Metalloproteinases
Transforming Growth Factor beta
Cell Movement
Cell Cycle
Cell Count
Cell Line
Messenger RNA
In Vitro Techniques

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Runx2, a target gene for activating transcription factor-3 in human breast cancer cells",
abstract = "Activating transcription factor (ATF-3) is a stress response gene and is induced by transforming growth factor beta 1 (TGF-β1) in breast cancer cells. In this study, we dissected the functional role of ATF-3 gene in vitro by knocking down its expression stably in human bone metastatic breast cancer cells (MDA-MB231). Knockdown of ATF-3 expression in these cells decreased cell number, altered cell cycle phase transition, and decreased mRNA expression of cell cycle genes. Knockdown of ATF-3 expression in MDA-MB231 cells also decreased cell migration, and the expression levels of invasive and metastatic genes such as MMP-13 and Runx2 were found to be decreased in these cells. Most importantly, ATF-3 was associated with Runx2 promoter in MDA-MB231 cells and knockdown of ATF-3 expression decreased its association with Runx2 promoter. Hence, our results suggested that ATF-3 plays a role in proliferation and invasion of bone metastatic breast cancer cells in vitro and we identified for the first time that Runx2 is a target gene of ATF-3 in MDA-MB231 cell line.",
author = "M. Gokulnath and Nicola Partridge and N. Selvamurugan",
year = "2015",
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language = "English (US)",
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AU - Gokulnath, M.

AU - Partridge, Nicola

AU - Selvamurugan, N.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Activating transcription factor (ATF-3) is a stress response gene and is induced by transforming growth factor beta 1 (TGF-β1) in breast cancer cells. In this study, we dissected the functional role of ATF-3 gene in vitro by knocking down its expression stably in human bone metastatic breast cancer cells (MDA-MB231). Knockdown of ATF-3 expression in these cells decreased cell number, altered cell cycle phase transition, and decreased mRNA expression of cell cycle genes. Knockdown of ATF-3 expression in MDA-MB231 cells also decreased cell migration, and the expression levels of invasive and metastatic genes such as MMP-13 and Runx2 were found to be decreased in these cells. Most importantly, ATF-3 was associated with Runx2 promoter in MDA-MB231 cells and knockdown of ATF-3 expression decreased its association with Runx2 promoter. Hence, our results suggested that ATF-3 plays a role in proliferation and invasion of bone metastatic breast cancer cells in vitro and we identified for the first time that Runx2 is a target gene of ATF-3 in MDA-MB231 cell line.

AB - Activating transcription factor (ATF-3) is a stress response gene and is induced by transforming growth factor beta 1 (TGF-β1) in breast cancer cells. In this study, we dissected the functional role of ATF-3 gene in vitro by knocking down its expression stably in human bone metastatic breast cancer cells (MDA-MB231). Knockdown of ATF-3 expression in these cells decreased cell number, altered cell cycle phase transition, and decreased mRNA expression of cell cycle genes. Knockdown of ATF-3 expression in MDA-MB231 cells also decreased cell migration, and the expression levels of invasive and metastatic genes such as MMP-13 and Runx2 were found to be decreased in these cells. Most importantly, ATF-3 was associated with Runx2 promoter in MDA-MB231 cells and knockdown of ATF-3 expression decreased its association with Runx2 promoter. Hence, our results suggested that ATF-3 plays a role in proliferation and invasion of bone metastatic breast cancer cells in vitro and we identified for the first time that Runx2 is a target gene of ATF-3 in MDA-MB231 cell line.

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