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Title page for ETD etd-04162012-131238


Type of Document Dissertation
Author Abreu, Maria Mercedes
Author's Email Address mariamercedesabreu@gmail.com
URN etd-04162012-131238
Title C/EBPbeta3 (LIP) induces cell death in breast cancer cells.
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Andries Zijlstra Committee Chair
Barbara FIngleton Committee Member
Linda Sealy Committee Member
Vito Quaranta Committee Member
Keywords
  • C/EBPbeta
  • breast cancer
  • cell death
  • autophagy
Date of Defense 2012-04-06
Availability unrestricted
Abstract
C/EBPbeta is a member of a family of basic-leucine zipper transcription factors. It has been shown to be a key regulator of growth and differentiation in the mammary gland. There are three different protein isoforms of C/EBPbeta. C/EBPbeta-1 and -2 are transactivators, and differ by just 23 N-terminal amino acids present in beta-1 only. C/EBPbeta-3 (LIP) lacks the transactivation domain and represses transcription. Overexpression of LIP is incompatible with cell proliferation and induces cell death in breast cancer cell lines. LIP expression stimulates autophagy, an evolutionarily conserved cellular process responsible for self-cannabalization through a lysosomal degradation pathway. Interestingly, I find that LIP expression not only leads to self-cannibalization in the MDA-MB-468 breast cancer cell line, but cell cycle profiling reveals a dramatic increase in DNA content in LIP expressing cells. I present data that the induction of autophagy appears to accompany or possibly follow the cannibalization or engulfment of neighboring cells by the LIP expressing cells. LIP expression was found to upregulate HSPA1A transcripts and concomitantly leads to increases in HSP70 protein levels in exosomes. Exosomes are 30- to 100-nm lipid bilayer vesicles that function to promote intercellular communication. LIP-derived exosomes appear to play a role in marking target cells for engulfment. Finally, I present data to show that LIP-induced cell engulfment may play a physiological role during involution of the mammary gland.

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