1. Academic Validation
  2. B7-H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells

B7-H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells

  • Cell Tissue Res. 2013 Jul;353(1):139-51. doi: 10.1007/s00441-013-1640-8.
Yun Qian 1 Bo Hong Ling Shen Zhigang Wu Hangping Yao Lihuang Zhang
Affiliations

Affiliation

  • 1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, 310003, Hangzhou, China. qianyunm@hotmail.com
Abstract

B7-H4 is expressed in a variety of tumor cells and functions as a negative regulator of T cells. However, clarification is needed as to whether B7-H4 mediates tumorigenesis through mechanisms, such as Apoptosis, in addition to mediating tumor immune escape. We investigate the mechanisms involved in enhanced oncogenicity and the inhibition of Apoptosis by B7-H4 in pancreatic Cancer cells. Short interfering RNAs (siRNAs) specific for B7-H4 were evaluated for their ability to knockdown B7-H4 mRNA and protein expression in pancreatic Cancer cells and the most effective siRNA was selected for investigating the effect of B7-H4 gene silencing in a number of functional assays. The inhibition of B7-H4 increased cell-cell adhesion and decreased the formation of pseudopodia. It also increased the expression of E-cadherin and decreased the expression of vimentin and CD44. B7-H4 siRNA inhibited cell proliferation, colony formation and migration of pancreatic Cancer cells. Moreover, increased Apoptosis in pancreatic Cancer cells following B7-H4 silencing was demonstrated in vitro by using flow cytometry and in a xenograft tumor model and was associated with increased Caspase activity and decreased ERK1/2 phosphorylation both in vitro and in vivo. Loss of B7-H4 function thus prevents tumor growth through many processes, including the induction of Apoptosis and inhibition of the ERK1/2 signaling pathway indicating that B7-H4 is a Cancer promoter and a potentially important therapeutic target. B7-H4 inhibition might offer an exciting opportunity to inhibit the progression of human pancreatic cancers.

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