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The role of the corepressor N-CoR1 related to TNF-alpha-mediated apoptosis in Breast cancer cells

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Abstract
We have investigated the role of Nuclear Receptor Corepressor1 (NCoR1) in Estrogen Receptor alpha (ERα) (+) breast cancer cells. The NCoR1 plays an important role in the Tumor Necrosis Factor-alpha (TNF-α)-mediated apoptosis. But, mechanism of ERα-NCoR1 complex is little known in breast cancer. Thus, we studied that TNF-α significantly down-regulates NCoR1 protein levels in ERα (+) MCF7 breast cancer cells. In addition, the reduced NCoR1 expression by TNF-α was induced the down-regulation of ERα protein levels in the MCF7 cells. This result suggests that NCoR1 expression may be involved in the TNF-α-mediated apoptosis of ERα (+) breast cancer cells. Interestingly, the phosphorylation of NCoR1 by Casein Kinase2 (CK2) inhibited the ubiquitin-dependent proteasomal degradation of NCoR1 in the TNF-α-treated MCF7 breast cancer cells. In conclusion, the down-regulation of NCoR1 and ERα by TNF-α induced the activation of Tumor suppressor p53 (p53). Thus, our results show that TNF-α treatment induces dissociation of ERα-NCoR1-p53 complex and activates p53-dependent pro-apoptosis target genes through the acetylation of p53.
These findings indicate that ERɑ-NCoR1-p53 complex represses the transcription activity of cell death genes, such as cyclin-dependent kinase inhibitor1 (p21), Bcl2-associated-X protein (Bax) and p53 upregulated modulator of apoptosis (Puma).

Keyword : Tumor Necrosis Factor-alpha (TNF-α), Estrogen Receptor alpha (ERα),
Nuclear Receptor Corepressor1 (NCoR1), Tumor suppressor p53 (p53), Apoptosis,
Breast cancer
Author(s)
박승호
Issued Date
2017
Awarded Date
2018-02
Type
Dissertation
URI
https://oak.ulsan.ac.kr/handle/2021.oak/6365
http://ulsan.dcollection.net/common/orgView/200000008681
Alternative Author(s)
Seung-Ho Park
Affiliation
울산대학교
Department
일반대학원 의학과의과학전공
Advisor
최경철
Degree
Master
Publisher
울산대학교 일반대학원 의학과의과학전공
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medical Science > 1. Theses (Master)
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