RT Journal Article
SR Electronic
T1 The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 6261
OP 6272
DO 10.4049/jimmunol.1301597
VO 191
IS 12
A1 Mimura, Kousaku
A1 Shiraishi, Kensuke
A1 Mueller, Anja
A1 Izawa, Shinichiro
A1 Kua, Ley-Fang
A1 So, Jimmy
A1 Yong, Wei-Peng
A1 Fujii, Hideki
A1 Seliger, Barbara
A1 Kiessling, Rolf
A1 Kono, Koji
YR 2013
UL http://www.jimmunol.org/content/191/12/6261.abstract
AB 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.