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.

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

“…It was recently reported that PI3K/AKT inhibitor inhibited the resistance to endocrine or DNA‐damaging radiotherapy in ER‐positive early patients with BC 31 . Besides, activation of the AKT pathway might also contribute to the radioresistance in BC and glioblastoma cells 13,26 . Consistent with this notion, our data show that the viability was increased in cells treated with LY294002 and radiation than in cells treated with radiation alone in the absence or presence of CPNE1 overexpression, suggesting that CPNE1 regulates TNBC radiosensitivity by regulating AKT activation.…”

“…31 Besides, activation of the AKT pathway might also contribute to the radioresistance in BC and glioblastoma cells. 13,26 Consistent with this notion, our data show that the viability was increased in cells treated with LY294002 and radiation than in cells treated with radiation alone in the absence or presence of CPNE1 overexpression, suggesting that CPNE1 regulates TNBC radiosensitivity by regulating AKT activation. However, whether DNA-damaging radiotherapy depends on the AKT signaling is still unknown.…”

“…It was previously reported that CPNE1 expression is upregulated in lung cancer, prostate cancer, and osteosarcoma; correlates with the survival of lung cancer and prostate cancer patients; and regulates tumorigenesis and chemoresistance 9‐12 . AKT pathway has been found to be associated with various cellular functions, including cell survival, motility, cell cycle progression, chemoresistance, and radioresistance 13,14 . CPNE1 can directly induce the differentiation of hippocampal progenitor cells via AKT phosphorylation 15 .…”

“…[9][10][11][12] AKT pathway has been found to be associated with various cellular functions, including cell survival, motility, cell cycle progression, chemoresistance, and radioresistance. 13,14 CPNE1 can directly induce the differentiation of hippocampal progenitor cells via AKT phosphorylation. 15 However, whether CPNE1 can regulate tumorigenesis and radiosensitivity in TNBC is not well understood.…”

New insights into radioresistance in breast cancer identify a dual function of miR‐122 as a tumor suppressor and oncomiR

“…RIPK1 (Miyamoto, ) and TNFRS21 (Benschop et al ., ) are components of the TNF pathway, whereas DUSP8 (Keyse, ) and HRAS (Knobbe et al ., ) act on the RAS‐MAPK pathway. Alteration in the activity of transcription factors could be critical for the development and maintenance of radioresistance in breast cancer by control genes of the survival pathways, such as the RAS‐MAPK and TNF pathways (Ishihara et al ., ; Zhao et al ., ). Many of the genes that we observed to be down‐regulated in the transcriptome analysis might be part of an epigenetic network of transcriptional silencing driven by axis miR‐122‐ ZNF611 or miR‐122‐ ZNF304 .…”