1. TGF-β and EGF induced HLA-I downregulation is associated with epithelial-mesenchymal transition (EMT) through upregulation of snail in prostate cancer cells.
- Author
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Chen, Xiao-Hui, Liu, Zong-Cai, Zhang, Ge, Wei, Wei, Wang, Xiao-Xiong, Wang, Hao, Ke, Hong-Peng, Zhang, Fan, Wang, Hong-Sheng, Cai, Shao-Hui, and Du, Jun
- Subjects
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PROSTATE cancer , *TRANSFORMING growth factors-beta , *EPIDERMAL growth factor , *HLA histocompatibility antigens , *GENETIC regulation , *EPITHELIAL cells , *CYTOTOXIC T cells - Abstract
Human leukocyte antigen class I antigens (HLA-I) is essential in immune response by presenting antigenic peptides to cytotoxic T lymphocytes. Downregulation of HLA-I is observed in primary and metastatic prostate cancers, which facilitates them escape from immune surveillance, thereby promotes prostate cancer progression. In addition, elevated level of growth factors like TGF-β or EGF in microenvironment is related to the prostate cancer deterioration. Thus, we wondered whether TGF-β or EGF was involved in the regulation of HLA-I during the development of prostate cancer cells. In this study, we demonstrated that TGF-β and EGF both downregulated the expression of HLA-I, thereby attenuated the cytotoxic T cell mediated lysis of prostate cancer cells. Next, we revealed that TGF-β and EGF induced downregulation of HLA-I is associated with classical epithelial-mesenchymal transition (EMT) morphological changes and expression profiles. We further illustrated that overexpression of Snail is crucial for HLA-I downregulation and its association with EMT. At last, we discussed that NF-κB/p65 is the plausible target for Snail to induce HLA-I downregulation. Taken together, this is the first evidence to reveal that both TGF-β and EGF can induce HLA-I downregulation which is then proven to be associated with EMT in prostate cancer cells. These discoveries provide a deeper understanding of growth factors induced immune escape and introduce potential therapeutic targets for prostate cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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