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Roles for epigenetic modifications at proinflammatory genes in tumor metastatasis
Author(s) -
Truax Agnieszka Dorota,
Greer Susanna Fletcher
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.457.7
Subject(s) - ciita , epigenetics , biology , major histocompatibility complex , cancer research , promoter , mhc class i , mhc class ii , transcription factor , microbiology and biotechnology , genetics , immune system , gene , gene expression
Epigenetic regulation is an essential mechanism by which cells regulate accessibility to chromatic DNA, hence allowing critical processes such as gene transcription to occur. The contribution of epigenetics to specific human cancers remains unknown. In order to achieve metastatic ability, tumors alter gene expression to escape host immunosurveilance. Major histocompatibility class II, MHC II, molecules are glycoproteins that present tumor derived antigens to CD4+ T cells and activate anti tumor immune responses. Thus, MHC II molecules are crucial for initiation and maintenance of the anti tumor response. MHC II molecules are regulated at the level of transcription by the Class II Transactivator, CIITA, whose association with the MHC II promoter is necessary to initiate MHC II transcription. To further understand the role played by epigenetics in regulating CIITA and MHC II expression in metastatic tumors, we have investigated histone modifications to CIITA and MHC II promoters in three variants of breast cancer line MDA MB435. We show that MHC II and CIITA expression are significantly down regulated in the highly metastatic variant which correlates with elevated levels of H3K27 trimethylation and decreased levels of H3 acetylation at the inducible CIITA promoter. Epigenetic changes are now thought to play important roles in the cancer progression. Research supported by GCC, ACS, GSU MBD.