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| Numb Inhibits the Ubiquitination Degradation of p53 by HDM2 in Triple-negative Breast Cancer |
Jie XIAN,Xue QIN,You-de CAO( ) |
| Teaching and Research Section of Pathology, School of Basic Medical Sciences, Medical University of Chongqing, Chongqing 400016, China |
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Abstract Objective : To investigate the decrease of Numb protein expression in triple-negative breast cancer patients and the effect of Numb protein on the p53 protein levels in triple-negative breast cancer and its regulation mechanism, and to further study the correlation between the decrease of Numb protein and the occurrence and development of triple-negative breast cancer, so as to provide a potential new therapeutic target for triple-negative breast cancer without effective treatment.Methods: 40 cases of triple negative breast cancer were taken from Clinical pathology diagnosis centre of Medical University of Chongqing. The expression of Numb protein in triple negative breast cancer patients was detected by immunohistochemistry. MCF-10A cell line and MDA-MB-231 cell line were all ATCC-derived. The mRNA and protein levels of Numb, HDM2 and p53 were compared by qPCR and Western blot. Numb was re-expressed in MDA-MB-231 cells by plasmid transfection. The expression of Numb, HDM2 and p53 was verified by qPCR and Western blot.Results: After transfection with NUMB-EGFP, the mRNA and protein levels of Numb in MDA-MB-231 cells were significantly increased, HDM2 did not change evidently, and p53 did not change significantly at the mRNA levels, but increased remarkably at the protein levels. The increased of Numb protein in NUMB-EGFP-transfected cells can regulate the p53 levels at post-transcriptional level, resulting in a significant increase of p53 protein levels.Conclusion: The expression of Numb protein in triple-negative breast cancer patients decreased by 55%, and Numb protein can regulate the level of p53 protein in triple-negative breast cancer cell line MDA-MB-231. The level of Numb protein is positively correlated with the level of p53 protein.
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Received: 16 January 2019
Published: 05 August 2019
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Corresponding Authors:
You-de CAO
E-mail: 420306100@qq.com
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