PRDM1 expression and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type
10.3760/cma.j.issn.0253-2727.2018.12.008
- VernacularTitle: 抑癌基因PRDM1在结外NK/T细胞淋巴瘤-鼻型中的表达及其与PI3K/AKT通路活化的关系
- Author:
Jumei LIU
1
;
Li LIANG
;
Sixia HUANG
;
Ting LI
Author Information
1. Department of Pathology, Peking University First Hospital, Beijing 100034, China
- Publication Type:Journal Article
- Keywords:
Phosphatidylinositol 3-kinase;
Protein kinases;
Lymphoma, extra-nodal NK-T-cell;
Genes, PRDM1
- From:
Chinese Journal of Hematology
2018;39(12):1010-1016
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression of PRDM1 and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type.
Methods:Immunocytochemistry and Western blot were used to detect the expression of PRDM1 and p-AKT in 10 EN-NK/T-NT tissue or 3 cell lines (PRDM1-positive YT cell line, PRDM1-negative NKL and NK92 cell lines). Nanostring gene expression profiling technique was used to detect the activation of the PI3K/AKT pathway in normal nasal mucosa, PRDM1-negative and positive EN-NK/T-NT tissue. MTS was used to detect cell proliferation, and flow cytometry was used to detect cell cycle and apoptosis.
Results:Nanostring gene expression profiling revealed that genes associated with PI3K/AKT signaling pathway (eg, IL-7, BRCA1, ITGA8, IL2RB, FASLG, CDK2, COL27A1, CSF3R, KITLG and IL-6) were highly expressed in EN-NK/T-NT cases (P<0.05). Also, we found that p-AKT was highly expressed in YT cell line, but lower or not expressed in NK92 and NKL cells. In addition, LY294002, a PI3K/AKT pathway inhibitor, increased PRDM1 and PTEN expression in a dose dependent manner in YT cells. More importantly, YT cell were treated with 20 μmol/L LY294002 48 h, the proliferation rate was significantly decreasing (58.18% vs 100.00%, t=12.770, P=0.006), and the proportion of cells in G1 phase was significantly increased (30.05% vs 76.93%, t=11.570, P<0.001). However, there was no significant difference in cell proliferation and cell cycle between NKL cells and control group (P>0.05).
Conclusion:The activation of PI3K/AKT pathway is positive associated with the expression of PRDM1 in EN-NK/T-NT, and inhibition of PI3K/AKT pathway may have significant therapeutic potential for PRDM1-positive EN-NK/T-NT.
