Abnormal Expression of c-Myc Oncogene in NK Cells in Patients with Cancer

被引:15
|
作者
Zakiryanova, Gulnur K. [1 ]
Kustova, Elena [2 ]
Urazalieva, Nataliya T. [2 ]
Baimuchametov, Emile T. [3 ]
Nakisbekov, Narymzhan N. [4 ]
Shurin, Michael R. [5 ,6 ]
机构
[1] Al Farabi Kazakh Natl Univ, Alma Ata 050040, Kazakhstan
[2] Sci Ctr Pediat & Children Surg, Immunol Lab, Alma Ata 050060, Kazakhstan
[3] Kazakh Res Inst Oncol & Radiol, Alma Ata 480072, Kazakhstan
[4] Asfendiyarov Kazakh Natl Med Univ, Atchabarov Sci Res Inst Fundamental & Appl Med, Joint Use Ctr, Alma Ata 050000, Kazakhstan
[5] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA
[6] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA 15213 USA
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 03期
关键词
NK cells; c-myc; MAPK; lung cancer; gastric cancer; NATURAL-KILLER-CELLS; ANTI-PD-1; DEFECTS; SAFETY; TISSUE;
D O I
10.3390/ijms20030756
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Natural killer (NK) cells have received a lot of attention in recent years for the roles they play in immunity and particularly in antitumor immune responses. Although defects in NK cell functions are recognized as important mechanisms for immune evasion of malignant cells, molecular pathways regulating NK cell dysfunction and exhaustion in cancer are largely unknown. Here we tested whether the c-myc proto-oncogene, known to promote cell proliferation, growth, differentiation, and apoptosis by regulating the expression of numerous target genes, may be involved in the mechanism of NK cell abnormalities in patients with lung and gastric cancer. Analysis of c-myc mRNA and protein expression in peripheral blood NK cells, mitogen-activated protein kinase (MAPK) activity, cell cycle, and cell longevity revealed a significantly decreased expression of c-myc mRNA and protein and mitotic arrest of NK cells in different phases of cell cycle. In addition, a significant decrease of NK cell death was also detected. These data allow the suggestion that defects of NK cell-mediated tumor surveillance may be associated with disturbed c-myc expression in NK cells in cancer patients. A better understanding of the mechanisms of NK cell dysfunction in cancer will help in the NK cell-mediated therapeutic eradication of primary and metastatic cancer cells and prolong patient survival.
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页数:11
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