High expression of PRKDC promotes breast cancer cell growth via p38 MAPK signaling and is associated with poor survival

Molecular Genetics & Genomic Medicine

Guo‐ming Wen¹  Da‐zhou Li²  Zhi‐liang Jing²  Guang‐long Liu²  Yan‐xia Wu²  Yong‐Jian Deng²  Min‐shan Tang²  Yan‐hua Li³  Yan Zhang³  Hongping Tang⁴  Wei‐kang Yang⁵  Chuan‐an Wu⁵ 

[1] Department of Outpatient Shenzhen Longhua District Maternity & Child Healthcare Hospital Shenzhen P.R. China;Department of Pathology Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University Guangzhou P.R. China;Department of Pathology Shenzhen Longhua District Maternity & Child Healthcare Hospital Shenzhen P.R. China;Department of Pathology Shenzhen Maternity & Child Healthcare Hospital Shenzhen P.R. China;Department of Prevention and Health Care Shenzhen Longhua District Maternity & Child Healthcare Hospital Shenzhen P.R. China;

关键词: breast cancer;    cell cycle;    cell proliferation;    p38 MAPK;    PRKDC;   

DOI  :  10.1002/mgg3.908

来源: DOAJ

【 摘 要 】

Abstract Background DNA‐Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression. Methods Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer. Results Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients’ data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF‐7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients. Conclusion Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.

【 授权许可】

Unknown