Runx2, a target gene for activating transcription factor-3 in human breast cancer cells
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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.
KeywordsATF-3 TGF-β1 MMP-13 Runx2 Bone metastasis
We thank S. Vimalraj for his technical help. This work was supported by the Indian Council of Medical Research, India (Grant No. 5/31/128/2009-NCD-III to N.S) and the Rajiv Gandhi National Fellowship (No. RGNF-2013-14-SC-TAM-42130 to M.G).
Conflicts of interest
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