HSPA12B: a novel facilitator of lung tumor growth.
HSPA12B: a novel facilitator of lung tumor growth.
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HSPA12B：肺肿瘤生长的新型促进剂
DOI：
10.18632/oncotarget.3533
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发表时间：
2015-04-30
期刊：
影响因子：
--
通讯作者：
Ding Z
中科院分区：
文献类型：
--
作者：
Ma H;Lu T;Zhang X;Li C;Xiong J;Huang L;Liu P;Li Y;Liu L;Ding Z
肺肿瘤的进展受促血管生成因子的调节。热休克蛋白A12 B（HSPA 12 B）是最近发现的一种促血管生成因子表达的调节因子。然而，HSPA 12 B是否在肺肿瘤生长中起作用尚不清楚。为了解决这个问题，将过表达HSPA 12 B的转基因小鼠（Tg）和野生型同窝小鼠（WT）植入刘易斯肺癌细胞以诱导肺肿瘤发生。与WT小鼠相比，Tg小鼠显示出显著更高的肿瘤数量和更大的肿瘤尺寸。与WT肿瘤相比，Tg肿瘤表现出血管生成和增殖增加，而凋亡减少。有趣的是，与WT肿瘤相比，在Tg肿瘤中检测到考克斯-2的显著增强的上调。此外，与WT肿瘤相比，Tg肿瘤表现出VEGF和血管生成素-1上调，AKAP 12下调，eNOS磷酸化增加。选择性考克斯-2抑制剂塞来昔布可抑制HSPA 12 B诱导的肺肿瘤负荷增加。此外，塞来昔布减少血管生成和增殖，而增加细胞凋亡的Tg肿瘤。此外，塞来昔布减少血管生成素-1表达和eNOS磷酸化，但增加AKAP 12水平在Tg肿瘤。我们的研究结果表明，HSPA 12 B通过考克斯-2依赖性机制刺激肺肿瘤生长。本研究确定HSPA 12 B作为一种新的促进肺肿瘤生长和治疗肺癌的潜在治疗靶点。
Lung tumor progression is regulated by proangiogenic factors. Heat shock protein A12B (HSPA12B) is a recently identified regulator of expression of proangiogenic factors. However, whether HSPA12B plays a role in lung tumor growth is unknown. To address this question, transgenic mice overexpressing HSPA12B (Tg) and wild-type littermates (WT) were implanted with Lewis lung cancer cells to induce lung tumorigenesis. Tg mice showed significantly higher number and bigger size of tumors than WT mice. Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT tumors. Interestingly, a significantly enhanced upregulation of Cox-2 was detected in Tg tumors than in WT tumors. Also, Tg tumors demonstrated upregulation of VEGF and angiopoietin-1, downregulation of AKAP12, and increased eNOS phosphorylation compared with WT tumors. Celecoxib, a selective Cox-2 inhibitor, suppressed the HSPA12B-induced increase in lung tumor burden. Moreover, celecoxib decreased angiogenesis and proliferation whereas increased apoptosis in Tg tumors. Additionally, celecoxib reduced angiopoietin-1 expression and eNOS phosphorylation but increased AKAP12 levels in Tg tumors. Our results indicate that HSPA12B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified HSPA12B as a novel facilitator of lung tumor growth and a potential therapeutic target for the treatment of lung cancer.
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影响因子：
8
作者：
Hoenerhoff, M. J.;Chu, I.;Barkan, D.;Liu, Z-y;Datta, S.;Dimri, G. P.;Green, J. E.
通讯作者：
Green, J. E.
影响因子：
9.2
作者：
Gelman, Irwin H.
通讯作者：
Gelman, Irwin H.
影响因子：
10.4
作者：
Shtivelband, MI;Juneja, HS;Wu, KK
通讯作者：
Wu, KK
影响因子：
15.9
作者：
D'Amico, Gabriela;Korhonen, Emilia A.;Alitalo, Kari
通讯作者：
Alitalo, Kari
影响因子：
158.5
作者：
Sandler, Alan;Gray, Robert;Johnson, David H.
通讯作者：
Johnson, David H.