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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 1 - 9 (9page)
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An F-box protein, β-TrCP recognizes substrate proteins and destabilizes them through ubiquitin-dependent proteolysis. It regulates the stability of diverse proteins and functions as either a tumor suppressor or an oncogene. Although the regulationby β-TrCP has been widely studied, the regulation of β-TrCP itself is not well understood yet. In this study, we found that the level of β-TrCP1 is downregulated by various protein kinase inhibitors in triple-negative breast cancer (TNBC) cells. A PI3K/mTOR inhibitor PI-103 reduced the level of β-TrCP1 in a wide range of TNBC cells in a proteasome-dependent manner. Concomitantly, the levels of c-Myc and cyclin E were also downregulated by PI-103. PI-103 reduced the phosphorylation of β-TrCP1 prior to its degradation. In addition, knockdown of β-TrCP1 inhibited the proliferation of TNBC cells. We furtheridentified that pharmacological inhibition of mTORC2 was sufficient to reduce the β-TrCP1 and c-Myc levels. These results suggest that mTORC2 regulates the stability of β-TrCP1 in TNBC cells and targeting β-TrCP1 is a potential approach to treathuman TNBC.
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참고문헌 (25)
참고문헌 신청
Brenton JD / 2005 / Molecular classification and molecular forecasting of breast cancer: ready for clinical application? / J Clin Oncol 23 : 7350 ~ 7360
Clark O / 2014 / Targeted therapy in triplenegative metastatic breast cancer : a systematic review and meta-analysis / Core Evid 9 : 1 ~ 11
Cross DA / 1995 / Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B / Nature 378 : 785 ~ 789
Folkes AJ / 2008 / The ident
Herold CI / 2013 / New targets for triple-negative breast cancer / Oncology 27 : 846 ~ 854
Clark O / 2014 / Targeted therapy in triplenegative metastatic breast cancer : a systematic review and meta-analysis / Core Evid 9 : 1 ~ 11
Cross DA / 1995 / Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B / Nature 378 : 785 ~ 789
Folkes AJ / 2008 / The ident
Herold CI / 2013 / New targets for triple-negative breast cancer / Oncology 27 : 846 ~ 854
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