Transcription factor ATF3 mediates the radioresistance of breast cancer.

Abstract

This study was designed to research the influence of activating transcription factor 3 (ATF3) on the radioresistance of breast cancer. ATF3 expression was measured by qRT-PCR and immunohistochemistry. Cancerous cell lines were cultured in vitro, and the expression of ATF3 was gauged by both qRT-PCR and Western blot before and after the radiation therapy. Cellular cycle and apoptosis were analysed by flow cytometry. Changes in the expression of corresponding proteins in the downstream pathways were identified by Western blot. Tumour xenograft was used to evaluate the effect of ATF3 in vivo. ATF3 was observed stronger in breast cancer tissues and cells. After radiation therapy, the expression of ATF3 in breast cancer cells was up-regulated. Silencing ATF3 could promote G2/M phase block, facilitate cell apoptosis and decrease clonogenic survival rate. The overexpression of ATF3 could curb G2/M-phase block, cell apoptosis and increase clonogenic survival rate. Overexpression ATF3 could increase radioresistance by up-regulating the level of phosphorylation of Akt in the PI3K/Akt signalling pathway. Radioresistance of breast cancer cells could be alleviated by inhibiting the PI3K/Akt signalling pathway. ATF3 could also promote radioresistance in vivo. ATF3 gene was able to promote radioresistance of breast cancer cells.

• Authors: Wenyan Zhao, Ming Sun, Shuqiang Li, Zhaofu Chen, Donghua Geng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 10 Pg. 4664-4675 (10 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 30117642 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• ATF3 protein, human
• Activating Transcription Factor 3
• Chromones
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Small Interfering
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Proto-Oncogene Proteins c-akt

Topics

• Activating Transcription Factor 3 (antagonists & inhibitors, genetics, metabolism)
• Animals
• Breast Neoplasms (genetics, mortality, pathology, therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects, radiation effects)
• Chromones (pharmacology)
• Female
• G2 Phase Cell Cycle Checkpoints (drug effects, genetics, radiation effects)
• Gamma Rays
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Radiation Tolerance (genetics)
• Signal Transduction
• Survival Analysis
• Tumor Burden (radiation effects)
• Xenograft Model Antitumor Assays