HSPA12B: a novel facilitator of lung tumor growth.

Lung tumor progression is regulated by proangiogenic factors. Heat shock protein A12B is a recently identified regulator of expression of proangiogenic factors. However, whether plays a role in lung tumor growth is unknown. To address this question, transgenic mice overexpressing Hduanyu184212B (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 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 Hduanyu184212B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified Hduanyu184212B as a novel facilitator of lung tumor growth and a potential therapeutic target for the treatment of lung cancer.

KEYWORDS: angiogenesis, apoptosis, heat shock protein A12B, lung cancer, proliferation