ArticleOncogene2008
Protein kinase C epsilon confers resistance of MCF-7 cells to TRAIL by Akt-dependent activation of Hdm2 and downregulation of p53.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.International journal of molecular sciences · 2024Review
- Upregulation of endogenous TRAIL-elicited apoptosis is essential for metformin-mediated antitumor activity against TNBC and NSCLC.Molecular therapy oncolytics · 2021Article
- A bismuth diethyldithiocarbamate compound induced apoptosis via mitochondria-dependent pathway and suppressed invasion in MCF-7 breast cancer cells.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells.International journal of molecular sciences · 2020Article
- Distinctive requirement of PKCε in the control of Rho GTPases in epithelial and mesenchymally transformed lung cancer cells.Oncogene · 2019Article
- Article
- Transcriptional regulation of oncogenic protein kinase Cϵ (PKCϵ) by STAT1 and Sp1 proteins.The Journal of biological chemistry · 2014Article
- Article
- Protein Kinase C-ε Promotes EMT in Breast Cancer.Breast cancer : basic and clinical research · 2014Article
- Systems Biology Strategy Reveals PKCδ is Key for Sensitizing TRAIL-Resistant Human Fibrosarcoma.Frontiers in immunology · 2014Article
- Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins.Molecular and cellular biochemistry · 2013Article
- Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family.Cell death and differentiation · 2013Review
- Breast cancer proteome takes more than two to tango on TRAIL: beat them at their own game.The Journal of membrane biology · 2012Review
- S6 kinase 2 promotes breast cancer cell survival via Akt.Cancer research · 2011Article
- Identification of Siah-interacting protein as a potential regulator of apoptosis and curcumin resistance.Oncogene · 2010Article
- Cancer/testis antigen CAGE exerts negative regulation on p53 expression through HDAC2 and confers resistance to anti-cancer drugs.The Journal of biological chemistry · 2010Article
- After damage of large bile ducts by gamma-aminobutyric acid, small ducts replenish the biliary tree by amplification of calcium-dependent signaling and de novo acquisition of large cholangiocyte phenotypes.The American journal of pathology · 2010Article
- Intracellular cleavage of osteopontin by caspase-8 modulates hypoxia/reoxygenation cell death through p53.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase C epsilon (PKC epsilon ) acts as an antiapoptotic protein and inhibits tumor necrosis factor-alpha (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in MCF-7 breast cancer cells. Members of the TNF receptor superfamily trigger apoptosis independent of the tumor suppressor protein p53, which primarily affects DNA damage-induced apoptosis. We have previously shown that PKC epsilon acts upstream of Akt to inhibit receptor-initiated cell death. Since Akt can regulate p53, we have examined the involvement of p53 in PKC epsilon-mediated TRAIL resistance. Overexpression of PKC epsilon in MCF-7 cells (MCF-7/PKC epsilon ) caused a decrease in p53 and an increase in human homolog of murine double minute 2 (Hdm2) and phospho-Hdm2. Depletion of p53 by siRNA attenuated, whereas depletion of Hdm2 enhanced TRAIL-mediated apoptosis. Knockdown of Akt decreased Hdm2 phosphorylation, increased p53 level and potentiated TRAIL-induced cell death. Depletion of epsilon from MCF-7 cells caused an increase in p53, whereas knockdown of p53 caused a decrease in Bid mRNA. Depletion of Akt from MCF-7/PKC epsilon cells resulted in an increase in p53 and Bid. These results suggest that PKC epsilon mediates TRAIL resistance by Akt-mediated phosphorylation of Hdm2 resulting in suppression of p53 expression and downregulation of Bid in MCF-7 breast cancer cells.
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