期刊论文详细信息
PLoS One
Proteomic Identification of Mitochondrial Targets of Arginase in Human Breast Cancer
Michael J. Haykinson1  Vikash Singh1  Nuraly K. Avliyakulov2  Meher Parveen3  Shehla Pervin3  Rajan Singh3  Gautam Chaudhuri3  Luis Martinez3  Melissa Braga4 
[1] Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America;Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America;Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, California, United States of America;Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
关键词: Mitochondria;    Breast tumors;    Breast cancer;    Protein expression;    Apoptosis;    Cancer treatment;    Gene expression;    Small interfering RNAs;   
DOI  :  10.1371/journal.pone.0079242
学科分类:医学(综合)
来源: Public Library of Science
PDF
【 摘 要 】

We have previously reported arginase expression in human breast cancer cells and demonstrated that the inhibition of arginase by Nω hydroxy L-arginine (NOHA) in MDA-MB-468 cells induces apoptosis. However, arginase expression and its possible molecular targets in human breast tumor samples and potential clinical implications have not been fully elucidated. Here, we demonstrate arginase expression in human breast tumor samples, and several established breast cancer cell lines, in which NOHA treatment selectively inhibits cell proliferation. The over-expression of Bcl2 in MDA-MB-468 cells abolished NOHA-induced apoptosis, suggesting that the mitochondria may be the main site of NOHA’s action. We, therefore, undertook a proteomics approach to identify key mitochondrial targets of arginase in MDA-MB-468 cells. We identified 54 non-mitochondrial and 13 mitochondrial proteins that were differentially expressed in control and NOHA treated groups. Mitochondrial serine hydroxymethyltransferase (mSHMT) was identified as one of the most promising targets of arginase. Both arginase II (Arg II) and mSHMT expressions were higher in human breast tumor tissues compared to the matched normal and there was a strong correlation between Arg II and mSHMT protein expression. MDA-MB-468 xenografts had significant upregulation of Arg II expression that preceded the induction of mSHMT expression. Small inhibitory RNA (siRNA)-mediated inhibition of Arg II in MDA-MB-468 and HCC-1806 cells led to significant inhibition of both the mSHMT gene and protein expression. As mSHMT is a key player in folate metabolism, our data provides a novel link between arginine and folate metabolism in human breast cancer, both of which are critical for tumor cell proliferation.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO201904026560116ZK.pdf 1472KB PDF download
  文献评价指标  
  下载次数:5次 浏览次数:13次