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HSPA12B: a novel facilitator of lung tumor growth.

Ma H, Lu T, Zhang X, Li C, Xiong J, Huang L, Liu P, Li Y, Liu L, Ding Z - Oncotarget (2015)

Bottom Line: Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

HSPA12B upregulated the expression of Cox-2, VEGF and Ang-1, increased the phosphorylation of eNOS, while decreased expression of AKAP12 in lung tumorsLung tumor tissues were collected 18 days after LLCs implantation. Protein extracts were prepared for immunoblotting with the indicated antibodies. The same membrane was blotted with α-Tubulin to serve as a loading control. All quantitative data are expressed as means ± SD. *P<0.01 and #P<0.05, n=4-6 per group.
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Figure 5: HSPA12B upregulated the expression of Cox-2, VEGF and Ang-1, increased the phosphorylation of eNOS, while decreased expression of AKAP12 in lung tumorsLung tumor tissues were collected 18 days after LLCs implantation. Protein extracts were prepared for immunoblotting with the indicated antibodies. The same membrane was blotted with α-Tubulin to serve as a loading control. All quantitative data are expressed as means ± SD. *P<0.01 and #P<0.05, n=4-6 per group.

Mentions: We recently reported that HSPA12B upregulates the expression of proangiogenic factors (e.g., VEGF, Ang-1 and eNOS) in the ischemic myocardium [5]. Because these proangiogenic factors play important roles in the regulation of angiogenesis, apoptosis proliferation [5, 10, 13, 14], their expression levels were examined in lung tumors. As shown in Figure 5A, the levels of VEGF, Ang-1 and eNOS were significantly increased in both WT and Tg tumors compared with the genotype-matched normal controls (P < 0.01 or P < 0.05), with significantly higher levels of VEGF and Ang-1 (16.7% and 78.2%, respectively) in Tg than in WT tumors (P < 0.01). Although eNOS levels were comparable between WT and Tg tumors, phospho-eNOS (p-eNOS) levels were 37.0% higher in Tg tumors than in WT tumors (P < 0.05).


HSPA12B: a novel facilitator of lung tumor growth.

Ma H, Lu T, Zhang X, Li C, Xiong J, Huang L, Liu P, Li Y, Liu L, Ding Z - Oncotarget (2015)

HSPA12B upregulated the expression of Cox-2, VEGF and Ang-1, increased the phosphorylation of eNOS, while decreased expression of AKAP12 in lung tumorsLung tumor tissues were collected 18 days after LLCs implantation. Protein extracts were prepared for immunoblotting with the indicated antibodies. The same membrane was blotted with α-Tubulin to serve as a loading control. All quantitative data are expressed as means ± SD. *P<0.01 and #P<0.05, n=4-6 per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496407&req=5

Figure 5: HSPA12B upregulated the expression of Cox-2, VEGF and Ang-1, increased the phosphorylation of eNOS, while decreased expression of AKAP12 in lung tumorsLung tumor tissues were collected 18 days after LLCs implantation. Protein extracts were prepared for immunoblotting with the indicated antibodies. The same membrane was blotted with α-Tubulin to serve as a loading control. All quantitative data are expressed as means ± SD. *P<0.01 and #P<0.05, n=4-6 per group.
Mentions: We recently reported that HSPA12B upregulates the expression of proangiogenic factors (e.g., VEGF, Ang-1 and eNOS) in the ischemic myocardium [5]. Because these proangiogenic factors play important roles in the regulation of angiogenesis, apoptosis proliferation [5, 10, 13, 14], their expression levels were examined in lung tumors. As shown in Figure 5A, the levels of VEGF, Ang-1 and eNOS were significantly increased in both WT and Tg tumors compared with the genotype-matched normal controls (P < 0.01 or P < 0.05), with significantly higher levels of VEGF and Ang-1 (16.7% and 78.2%, respectively) in Tg than in WT tumors (P < 0.01). Although eNOS levels were comparable between WT and Tg tumors, phospho-eNOS (p-eNOS) levels were 37.0% higher in Tg tumors than in WT tumors (P < 0.05).

Bottom Line: Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus