Abstract
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. Here, we report that LIP expression stimulates autophagy and induces cell death in breast cancer cell lines. Overexpression of LIP is incompatible with cell growth and when cell cycle analysis was performed in the LIP-MDA-MB-231 breast cancer cell line, a DNA profile of cells undergoing apoptosis was not observed. Instead, LIP expressing cells appeared to have large autophagic vesicles when examined via electron microscopy. Autophagy is an evolutionarily conserved cellular process responsible for self-cannabalization through a lysosomal degradation pathway. Autophagy was further assessed in LIP expressing and control breast cancer cells by monitoring the development of acidic vesicular organelles and conversion of LC3 from the cytoplasmic form to the autophagosome form. LIP expression leads to an increase in acidic vesicles. In addition, activation of LC3 was detected in LIP expressing cells by immunoblot analysis and immunofluorescence studies. Interestingly, we find that LIP expression not only leads to massive and rapid cell death in the MDA-MB-468 breast cancer cell line, but cell cycle profiling reveals a dramatic increase in DNA content in LIP expressing cells. We present data that the induction of autophagy appears to accompany or possibly follow the engulfment of neighboring cells by the LIP expressing cells. Recently, there have been reports of different cell death processes that occur due to cell internalization. LIP overexpression may be one important factor that is driving cell engulfment resulting in cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4978. doi:1538-7445.AM2012-4978
Published Version
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