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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04162012-131238 |
| Date | 03 May 2012 |
| Creators | Abreu, Maria Mercedes |
| Contributors | Andries Zijlstra, Vito Quaranta, Barbara FIngleton, Linda Sealy |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf, video/quicktime |
| Source | http://etd.library.vanderbilt.edu/available/etd-04162012-131238/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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