Journal
ONCOTARGET
Volume 6, Issue 12, Pages 9924-9936Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3533
Keywords
heat shock protein A12B; lung cancer; angiogenesis; proliferation; apoptosis
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Funding
- National Natural Science Foundation of China [81370260, 81371450, 81301616, 81170321]
- Jiangsu Province's Outstanding Medical Academic Leader program [LJ201124]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine
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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 wildtype 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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