ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Involvement of FLIP in 2-methoxyestradiol-induced tumor regression in transgenic adenocarcinoma of mouse prostate model.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- The β-1,4 GalT-V Interactome-Potential Therapeutic Targets and a Network of Pathways Driving Cancer and Cardiovascular and Inflammatory Diseases.International journal of molecular sciences · 2025Review
- The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.Biomedicines · 2024Review
- Evidence for 2-Methoxyestradiol-Mediated Inhibition of Receptor Tyrosine Kinase RON in the Management of Prostate Cancer.International journal of molecular sciences · 2021Article
- High-level Sp1 is Associated with Proliferation, Invasion, and Poor Prognosis in Astrocytoma.Pathology oncology research : POR · 2019Article
- Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans.Molecular carcinogenesis · 2019Article
- WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP.Cancers · 2019Article
- BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions.International journal of molecular sciences · 2018Article
- The estrogen metabolite 2-methoxyestradiol regulates eukaryotic initiation factor 4E (eIF4E) and inhibits protein synthesis in MG63 osteosarcoma cells.Genes & diseases · 2016Article
- Crosstalk between RON and androgen receptor signaling in the development of castration resistant prostate cancer.Oncotarget · 2016Article
- Opportunities and challenges in combination gene cancer therapy.Advanced drug delivery reviews · 2016Review
- Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95.Oncotarget · 2016Article
- 2ME2 inhibits the activated hypoxia-inducible pathways by cabozantinib and enhances its efficacy against medullary thyroid carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Targeted NF1 cancer therapeutics with multiple modes of action: small molecule hormone-like agents resembling the natural anticancer metabolite, 2-methoxyoestradiol.British journal of cancer · 2015Article
- Palmatine inhibits growth and invasion in prostate cancer cell: Potential role for rpS6/NFκB/FLIP.Molecular carcinogenesis · 2015Article
- Activation of AKR1C1/ERβ induces apoptosis by downregulation of c-FLIP in prostate cancer cells: A prospective therapeutic opportunity.Oncotarget · 2015Article
- NQO1 suppresses NF-κB-p300 interaction to regulate inflammatory mediators associated with prostate tumorigenesis.Cancer research · 2014Article
- Senescence-secreted factors activate Myc and sensitize pretransformed cells to TRAIL-induced apoptosis.Aging cell · 2014Article
- Combined targeting of STAT3/NF-κB/COX-2/EP4 for effective management of pancreatic cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Dietary resveratrol prevents development of high-grade prostatic intraepithelial neoplastic lesions: involvement of SIRT1/S6K axis.Cancer prevention research (Philadelphia, Pa.) · 2013Article
- Control of FLIP(L) expression and TRAIL resistance by the extracellular signal-regulated kinase1/2 pathway in breast epithelial cells.Cell death and differentiation · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe purpose of this study is to investigate whether Fas-associated death domain interleukin-1 converting enzyme like inhibitory protein (FLIP) inhibition is a therapeutic target associated with 2-methoxyestradiol (2-ME2)-mediated tumor regression. EXPERIMENTAL
designExpression and levels of FLIP were analyzed using (a) real-time PCR and immunoblot analysis in androgen-independent PC-3 cells treated with the newly formulated 2-ME2 and (b) immunohistochemistry in different Gleason pattern human prostate tumors. Transient transfections and chromatin immunoprecipitation (ChIP) assays were used to identify the transcription factors that regulate FLIP. Involvement of FLIP in 2-ME2-induced tumor regression was evaluated in transgenic adenocarcinoma mouse prostate (TRAMP) mice.
resultsHigh Gleason pattern (5+5) human prostate tumors exhibit significant increase in FLIP compared with low Gleason pattern 3+3 (P=or<0.04). 2-ME2 reduced the levels and promoter activity of FLIP (P=0.001) in PC-3 cells. Transient expression assays show sequences between -503/+242 being sufficient for 2-ME2-induced inhibition of FLIP promoter activity. Cotransfection experiments show that overexpression of Sp1 activated, whereas Sp3 inhibited, Sp1 transactivation of FLIP promoter activity (P=0.0001). 2-ME2 treatment reduced binding of Sp1 to the FLIP promoter as evidenced by ChIP. Further, levels of FLIP associated with Fas or FADD decreased, whereas cleavage of caspase-8, levels of Bid, and apoptosis increased in response to 2-ME2 treatment in PC-3 cells. Administration of 2-ME2 regressed established prostate tumors in TRAMP mice that were associated with reduced expression of FLIP and Sp1.
conclusionTargeting Sp1-mediated FLIP signaling pathway may provide a novel approach for prostate cancer management.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.