Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway.
Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage ( p = 0.027), positive regional lymph node metastasis ( p = 0.002), and poor overall survival ( p = 0.002). Proliferation assay results showed that Noxin obviously promoted the ability of proliferation of normal breast cells. Subsequent western blot results revealed that Cyclin D1 and Cyclin E1 were upregulated by overexpressing Noxin, whereas Cyclin D1 and Cyclin E1 were downregulated after depleting Noxin. The levels of phosphorylated P38 and activating transcription factor 2 were obviously increased after overexpressing Noxin, and their expression was downregulated accordingly by transfecting Noxin-small interfering RNA. Moreover, P38 inhibitor counteracted the elevating expression of phosphorylated activating transcription factor 2, Cyclin D1, and Cyclin E1 induced by Noxin overexpression and thereby reversed the effect of Noxin overexpression on facilitating cell growth. Taken together, our studies indicated that Noxin was overexpressed in breast cancer and its positive expression was significantly correlated with advance tumor-node-metastasis stage, positive lymph node metastasis, and poor prognosis. Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer.
['Zhang|Xiupeng|X|', 'Zhang|Yong|Y|', 'Fan|Chuifeng|C|', 'Wang|Liang|L|', 'Liu|Yang|Y|', 'Li|Ailin|A|', 'Jiang|Guiyang|G|', 'Zhou|Haijing|H|', 'Cai|Lin|L|', 'Miao|Yuan|Y|']
D051698:Activating Transcription Factor 2 D000328:Adult D017209:Apoptosis D051017:Apoptosis Regulatory Proteins D001943:Breast Neoplasms D002453:Cell Cycle D018797:Cell Cycle Proteins D049109:Cell Proliferation D019938:Cyclin D1 D019927:Cyclin E D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008207:Lymphatic Metastasis D061986:MCF-7 Cells D008875:Middle Aged D009367:Neoplasm Staging D015513:Oncogene Proteins D034741:RNA, Small Interfering D015398:Signal Transduction D048051:p38 Mitogen-Activated Protein Kinases
Noxin proliferation breast cancer P38 prognosis