Runx2, a target gene for activating transcription factor-3 in human breast cancer cells.
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.
Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, 603203, Tamil Nadu, India.
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M
Gokulnath
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NC
Partridge
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N
Selvamurugan
D051700:Activating Transcription Factor 3 / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics
C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D053773:Transforming Growth Factor beta1; D053509:Matrix Metalloproteinase 13