Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth
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Taylor B. Turner1, Selene Meza-Perez2, Angelina Londoño3, Ashwini Katre1, Jacelyn E. Peabody4, Haller J. Smith1, Andres Forero5, Lyse A. Norian6, J. Michael Straughn Jr1, Donald J. Buchsbaum3, Troy D. Randall2 and Rebecca C. Arend1
1Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA
2Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
3Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA
4NIH Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA
5Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama, USA
6Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
Taylor B. Turner, email: [email protected]
Keywords: epigenetics, ovarian cancer, MHC II, HDACi, DNMTi
Received: January 09, 2017 Accepted: April 10, 2017 Published: April 24, 2017
Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators – histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent. A dose dependent response in mRNA and protein expression was seen with entinostat. Combination treatment showed higher MHC II protein expression than with single agent treatment. In patient derived xenografts, CIITA, CD74, and MHC II mRNA transcripts were significantly increased after combination treatment. Expression of MHC II on ovarian tumors in MISIIR-Tag mice was increased with both agents relative to control. Combination treatment significantly reduced ID8 tumor growth in immune-competent mice. Epigenetic treatment increases expression of MHC II on ovarian cancer cells and impedes tumor growth. This approach warrants further study in ovarian cancer patients.
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