Please use this identifier to cite or link to this item:
|Title:||The MAPK pathway is a predominant regulator of HLA-A expression in esophageal and gastric cancer||Authors:||Mimura, K.
|Issue Date:||15-Dec-2013||Citation:||Mimura, K., Shiraishi, K., Mueller, A., Izawa, S., Kua, L.-F., So, J., Yong, W.-P., Fujii, H., Seliger, B., Kiessling, R., Kono, K. (2013-12-15). The MAPK pathway is a predominant regulator of HLA-A expression in esophageal and gastric cancer. Journal of Immunology 191 (12) : 6261-6272. ScholarBank@NUS Repository. https://doi.org/10.4049/jimmunol.1301597||Abstract:||Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag-specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer. Copyright © 2013 by The American Association of Immunologists, Inc.||Source Title:||Journal of Immunology||URI:||http://scholarbank.nus.edu.sg/handle/10635/117191||ISSN:||00221767||DOI:||10.4049/jimmunol.1301597|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Oct 20, 2021
WEB OF SCIENCETM
checked on Oct 20, 2021
checked on Oct 14, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.