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Archive > Volume 24 Issue 8 > 2017,24(8):845-850. DOI:10.3872/j.issn.1007-385X.2017.08.005 Prev Next
Basic Research
The effect of DNAJ heat shock protein family member B8 gene on lung adenocar-cinoma invasion and metastasis and its possible mechanism
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Abstract:
Objective: To explore the expression of DNAJB8 （DnaJ heat shock protein family (Hsp40) member B8）in lung adenocarcinoma tissues and its effect on the invasion and migration of lung adenocarcinoma cells. Methods:102 surgical specimens resected from lung adenocarcinoma surgeries from 2006 to 2008 were collected at Sichuan Provincial People's Hospital, the expression of DNAJB8 in lung adenocarcinoma tissues was determined by immu-nohistochemistry (IHC), and its relationships with clinical pathological parameters and prognosis were analyzed.A549 cells with stable DNAJB8 knock down and H1299 cells with stable DNAJB8 overexpression were estab-lished; the effect of knockdown or overexpression of DNAJB8 on the proliferation of lung adenocarcinoma cells was evaluated by CCK-8 assay, the effect on the invasion ability of lung adenocarcinoma cells was determined us-ing Transwell assay, and the expression of invasion related proteins including MMP-2, MMP-9 and ERK were deter-mined by Western blotting; A xenograft model of lung adenocarcinoma was constructed on nude mice by injecting A549 cells with DNAJB8 knockdown via the tail vein to observe the effect of DNAJB8 on the migration of A549 cells in vivo. Results: The level of DNAJB8 expression in lung adenocarcinoma tissues was significantly higher than that in normal lung tissues, the high expression was positively correlated with lymph node metastasis and TNM staging, and predicted poor prognosis (P<0.01). The expression of DNAJB8 in A549 cells was higher than that in H1299 cells, and down-regulation of DNAJB8 expression inhibited the invasion of A549 cells ([41±3] vs [192±11]，P<0.01), while up-regulation of DNAJB8 promoted the invasion of H1299 cells ([235±14] vs [25±4]，P<0.01). The number of lung tumors in the mice of experimental group was significantly lower than that in the control group ([5±1] vs [17±3]，P<0.01). After DNAJB8 knockdown in A549 cells, the expressions of MMP-2, MMP-9 and p-ERK were decreased significantly (P<0.01); however, after the overexpression of DNAJB8 in H1299 cells, the expression of MMP-2, MMP-9 and p-ERK were significantly increased (P<0.01). Conclusion: DNAJB8 could promote the in-vasion and metastasis of lung adenocarcinoma cells, which is likely related with the MEK/Erk signaling pathway.
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Project Supported:
Project supported by Science and Technology Department Foundation of Sichuan Prov-ince (No.2014SZ0055)
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