C/EBP(Beta) Isoforms - An Innovative Transcription Factor Therapy for Breast Cancer.

摘要

The transcription factor, C/EBPbeta, is critical for growth and differrentation of the mammary gland. Three forms of C/EBPbeta are expressed in cells through alternative translation of the C/EBPbeta mRNA. C/EBPbeta- 1 and -2 activate transcription; C/EBPbeta-2 is a truncated form that represses transcription. Based upon their distinct expression patterns in normal and transformed cells as well as functional studies, we propose that C/EBPbeta-l and -3 (or both) will be potent anti-tumor therapies when used either singly or in combination by suppressing the expression of genes which drive the cell cycle (C/EBPbeta-3) and/or reactivating a differentiation program (C/EBPbeta-1). The purpose of this study is to develop non-replicating murine retroviral and adenoviral vectors carrying genes selectively encoding either C/EBPbeta-l or -3. These vectors will be used to efficiently re-express C/EBPbeta-l and/or overexpress C/EBPbeta-3 in breast cancer cells lines and evaluate the growth potential of the cells. We have successfully generated murine retroviral vectors encoding C/EBPbeta-l and C/EBPbeta-3 as well as an adenovirus encoding C/ ebpbeta-3. We have infected breast cancer cell lines with each of these viruses and documented nuclear expression of C/EBPbeta-l and -3 by both immunohistochemistry and immunoblotting. Studies on the growth potential of the infected cells are confidential and will be presented in the annual report.