Effect of MHC Class II Transactivator (CIITA) on the Growth and Metastasis of Breast Tumors

摘要

CIITA is a recently described protein that up regulates several different genes involved in the MHC class II antigen presentation pathway. I hypothesize that the de novo expression of molecules involved in the MHC class II antigen presentation pathway may render the tumor cells immunogenic and lead to tumor rejection. Also, preliminary data in our lab has revealed that, in addition to its effects on class II genes, CIITA is also able to induce MHC class I genes in tumor cell lines that have low or no expression of these molecules. Given that early studies have shown that de novo expression of syngeneic MHC class I genes in some tumors can induce tumor immunity and that approximately 33% of breast tumors have downmodulated class I expression, CIITA may be an effective molecule for the induction of tumor immunity via MHC class I and class II. The induction of tumor immunity using a global transactivator is a novel therapeutic strategy. I propose to accomplish these goals with two aims: 1) Determination of the genes induced by CIITA in breast carcinoma cell lines. 2) Determination of the effect of CIITA expression in breast carcinoma cell lines on in vivo growth, metastasis and vaccine efficacy.