2017
DOI: 10.18632/oncotarget.20408
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Abstract: A critical problem in leukemia as well as other cancer therapies is the development of chemotherapeutic drug-resistance. We have developed models of hematopoietic drug resistance that are based on expression of dominant-negative TP53 [TP53 (DN)] or constitutively-active MEK1 [MEK1(CA)] oncogenes in the presence of chemotherapeutic drugs. In human cancer, functional TP53 activity is often lost in human cancers. Also, activation of the Raf/MEK/ERK pathway frequently occurs due to mutations/amplification of upstr… Show more

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Cited by 16 publications
(22 citation statements)
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References 148 publications
(157 reference statements)
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“…Previously, we and others have examined the roles of TP53 in the sensitivity of hematopoietic, prostate and pancreatic cells and other cancer types to chemotherapeutic drugs and, in some cases, radiation (Lehmann et al, 2007' McCubrey et al, 2008Chappell et al, 2012;Abrams et al, 2017;Steelman et al, 2017;Abrams et al, 2018;Abrams et al, 2019). We observed that introduction of dominant negative (DN)-TP53 into FL5.12 hematopoietic cells increased their chemoresistance (McCubrey et al, 2008;Abrams et al, 2017;Steelman et al, 2017). The biological effects of addition of WT-TP53 or DN-TP53 to cells which either lack or have WT-TP53 have been examined in prostate cancer cells (Lehmann et al, 2007;Chappell et al, 2012).…”
Section: Pancreatic Cancer Genetics: Some Common Oncogenes/tumor Suppmentioning
confidence: 99%
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“…Previously, we and others have examined the roles of TP53 in the sensitivity of hematopoietic, prostate and pancreatic cells and other cancer types to chemotherapeutic drugs and, in some cases, radiation (Lehmann et al, 2007' McCubrey et al, 2008Chappell et al, 2012;Abrams et al, 2017;Steelman et al, 2017;Abrams et al, 2018;Abrams et al, 2019). We observed that introduction of dominant negative (DN)-TP53 into FL5.12 hematopoietic cells increased their chemoresistance (McCubrey et al, 2008;Abrams et al, 2017;Steelman et al, 2017). The biological effects of addition of WT-TP53 or DN-TP53 to cells which either lack or have WT-TP53 have been examined in prostate cancer cells (Lehmann et al, 2007;Chappell et al, 2012).…”
Section: Pancreatic Cancer Genetics: Some Common Oncogenes/tumor Suppmentioning
confidence: 99%
“…Chemotherapy can induce TP53 and NF-κB and other molecules such as Raf/MEK/ERK and PI3K/PTEN/AKT/mTOR and other pathways which are involved in the resistance to multiple therapeutic approaches (Abrams et al, 2017;Steelman et al, 2017). Many signaling pathways, nutraceuticals and natural products interact with NF-κB and TP53 and other pathways which are involved with drug resistance (McCubrey et al, 2017(McCubrey et al, , 2018.…”
Section: Targeting Signal Transduction Pathways Induced By Chemotherapymentioning
confidence: 99%
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“…Nutraceuticals, chemotherapeutic drugs, signal transduction inhibitors were purchased from either Selleckchem (Houston, TX USA) or Sigma-Aldrich (Saint Louis, MO, USA). MIA-PaCa- Candido et al Advances in Biological Regulation xxx (2018) xxx-xxx 2 and MCF-7 cells were titrated with the different nutraceuticals, signal transduction inhibitors, chemotherapeutic and other drugs as described (Chappell et al, 2012;Abrams et al, 2017;Steelman et al, 2018). Statistical analysis was performed using GraphPad Prism.…”
Section: Tissue Culture and Treatment Of Cells With Signal Transductimentioning
confidence: 99%
“…Because several key elements of this pathway have been found mutated in cancer, much emphasis has been placed on developing drugs which target PI3K signaling (Fransecky et al, 2015;Fragoso and Barata, 2017;Ruvolo, 2017;Park et al, 2010), leading to a number of molecules being trialled in several malignancies, including AML. While it is well established that over 60% of AML patients show increased activity of PI3K/AKT signaling (Park et al, 2010;Bertacchini et al, 2014Bertacchini et al, , 2015, its relationship with resistance to therapy is not completely settled (Abrams et al, 2017;Marmiroli et al, 2015). Previous studies by us and others showed that aberrant signaling by the abovementioned pathway modulates expression of the MDR1 gene in acute leukemia (Tazzari et al, 2007;Seo et al, 2010).…”
Section: Introductionmentioning
confidence: 99%