Download Title Hypoxia-inducible factor-1α dependent cytoplasmic B7

< Abstract >
Title Hypoxia-inducible
factor-1α dependent cytoplasmic
B7-H4 promotes proliferation of cancer cells through IL-8
upregulation.
You-kyoung Jeon, Hana Kim and Inhak Choi.
Department of microbiology and Immunology, Advanced Research Cencer for Multiple myeloma,
Inje University College of Medicine, Busan 614-735
B7-H4 is a co-signaling molecule which has an inhibitory effect on T cell functions. Its
expression on cancer tissues has been suggested to correlated with poor survival of cancer
patients, indicating that B7-H4 is a critical immune checkpoint in anti-cancer immunity.
However, there are few reports regarding the regulation of B7-H4 expression on cancer cells.
In the present study, we observed that B7-H4 expression was induced in the cytoplasm, but
not on surface, of cancer cells under hypoxia. This notion was further supported by the
observations showing that transfection of hypoxia inducible factor-1α (HIF-1 α) gene induces
B7-H4 expression and treatment of HIF-1 α inhibitor decreased its expression. Furthermore,
using B7-H4 promoter-luciferase construct, we found that B7-H4 promoter activity was greatly
enhanced under hypoxia compared to normoxia. To investigate the function of hypoxiainduced B7-H4, we used B7-H4 knockdown KMS cell line and HeLa cell line. Silencing of B7H4 decreased proliferation in hypoxia as evidenced by the findings that hypoxic cells showed
the reduction of S-phase in cell cycle, but not apoptosis, indicating that HIF-1α-induced B7H4 regulate proliferation.
References
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L. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity.
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[2] Yu N1, Li X, Zheng S, Li X. B7-H4's role "beyond the tumor". Inflammation. 2013 Aug;36(4):941-7.
[3] Zhang L1, Wu H, Lu D, Li G, Sun C, Song H, Li J, Zhai T, Huang L, Hou C, Wang W, Zhou B, Chen
S, Lu B, Zhang X.The costimulatory molecule B7-H4 promote tumor progression and cell proliferation
through translocating into nucleus. Oncogene 2013 Nov 14;32(46):5347-58.
Keywords
B7-H4, hypoxia, HIF-1α, proliferation, IL-8