The Effect of MHC Class II Transactivator on the Growth and Metastasis of Breast Tumors
Annual rept. 1 Jun 98-31 May 99
NORTH CAROLINA UNIV AT CHAPEL HILL
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I have continued my investigations into the effect of the MHC class II transactivator, CIITA, on the growth and immunogenicity in breast cancer. I have utilized three different model systems MT90 1, 4T 1 and EMT6. In the MT90 1 cell line, CIITA expression does not change in vivo tumor growth properties. In the 4T1 model, expression of CIITA leads to direct killing of the tumor in vitro, suggesting that CIITA has a toxic effect in this cell line. We are actively investigating inducible CIITA expression systems to fully investigate this phenomenon. We have also investigated immunogenicity of CIITA expressing tumors. MT9Ol is immunogenicand cannot be used in these assays, therefore we have used the Line 1 lung carcinoma as a surrogate system we have also started to examine EMT6 as an additional mammary tumor model. We have found that CIITA expression can result in more mice with tumor formation, suggesting a negative role for CIITA in the absence of costimulation. We have initiated preliminary investigations into novel genes induced by CIITA. The results of these experiments have important implications in proposed CIITA-human gene therapy trials.
- Medicine and Medical Research