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FUNCTIONAL ANALYSIS OF C/EBPδ IN MAMMARY EPITHELIAL CELLS AND MOLECULAR MECHANISMS OF MYC-INDUCED C/EBPδ REPRESSION

Si, Junling
http://rave.ohiolink.edu/etdc/view?acc_num=osu1242757954

Abstract Details

2009, Doctor of Philosophy, Ohio State University, Veterinary Biosciences.
C/EBPδ is a highly conserved basic region leucine zipper (bZip) DNA binding protein and plays important roles in regulating proliferation and differentiation of mammary epithelial cells. “Loss of function” alterations in C/EBPδ expression have been reported in mammary tumorigenesis. In this study, the role of C/EBPδ in normal mammary epithelial cells (MECs), the defects in C/EBPδ growth inhibitory signaling pathway MECs acquired during progression from normal to malignant cells and the molecular mechanisms of Myc-induced C/EBPδ repression were investigated.The role of IL-6/STAT3/C/EBPδ signal transduction pathway in response to growth arrest treatments was investigated in normal and transformed MECs. While growth arrest treatments activated IL-6/STAT3 pathway and induced CEBPδ expression in non-transformed MECs, growth arrest treatments failed to activate IL-6/STAT3/CEBPδ pathway in transformed MECs and lead to defective growth arrest. The influence of C/EBPδ expression on MECs was also investigated using RNA interference. Our results revealed that loss of C/EBPδ expression in MECs leads to impaired growth arrest and defective differentiation. We also observed that C/EBPδ expression in MECs is repressed by c-Myc in a dose-dependent manner under growing conditions and that c-Myc-induced C/EBPδ repression is released under growth arrest conditions. The molecular mechanism of c-Myc-induced C/EBPδ transcriptional repression was investigated using c-Myc mutants and RNA interference. Our results suggested that Myc box 2 and helix-loop-helix/leucine zipper domains of c-Myc are implicated in C/EBPδ repression.
James DeWille, PhD (Advisor)
Steven Weisbrode, DVM,PhD (Committee Member)
Nongnuch Inpanbutr, DVM,PhD (Committee Member)

Recommended Citations

Citations

  • Si, J. (2009). FUNCTIONAL ANALYSIS OF C/EBPδ IN MAMMARY EPITHELIAL CELLS AND MOLECULAR MECHANISMS OF MYC-INDUCED C/EBPδ REPRESSION [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1242757954

    APA Style (7th edition)

  • Si, Junling. FUNCTIONAL ANALYSIS OF C/EBPδ IN MAMMARY EPITHELIAL CELLS AND MOLECULAR MECHANISMS OF MYC-INDUCED C/EBPδ REPRESSION. 2009. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1242757954.

    MLA Style (8th edition)

  • Si, Junling. "FUNCTIONAL ANALYSIS OF C/EBPδ IN MAMMARY EPITHELIAL CELLS AND MOLECULAR MECHANISMS OF MYC-INDUCED C/EBPδ REPRESSION." Doctoral dissertation, Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1242757954

    Chicago Manual of Style (17th edition)

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© 2009, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.