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

• Published in: Tumor biology Vol. 36; no. 3; pp. 1923 - 1931
• Main Authors: Gokulnath, M., Partridge, N. C., Selvamurugan, N.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2015; Springer Nature B.V
• Subjects: Activating Transcription Factor 3 - genetics; Biomedical and Life Sciences; Biomedicine; Bones; Breast cancer; Breast Neoplasms - genetics; Cancer Research; Cell adhesion & migration; Cell Cycle - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Core Binding Factor Alpha 1 Subunit - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 13 - genetics; Metastasis; Neoplasm Metastasis; Promoter Regions, Genetic; Research Article; RNA, Messenger - genetics; Transforming Growth Factor beta1 - genetics; MMP-13; TGF-β1; ATF-3; Bone metastasis; Runx2
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2796-x

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.