Description(s):

Epidermal growth factor receptor (EGFR) is a cell-surface receptor with intrinsic intracellular protein-tyrosine kinase (TK) activity. Ligand binding induces EGFR dimerization and phosphorylation, leading to the activation of EGFR signaling pathway. In several malignancies such as non-small cell lung cancer (NSCLC), EGFR signaling is deregulated due to mutations in EGFR, which results in uncontrolled proliferation and migration of tumor cells. EGFR mutations can lead to “oncogene-addicted” cancers, where the tumor cells depend on the mutated EGFR for cell survival and malignant phenotype.  One of the most common EGFR mutations found in human patients is L858R substitution in exon 21, within the activation loop of EGFR. Patients with this mutation are sensitive to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib, whereas patients with wild type EGFR are not sensitive to TKI. Another clinically relevant mutation associated with acquired gefitinib and erlotinib resistance is T790M, found in exon 20. Cells expressing EGFR with both L858R and T790M mutations are resistant to induced apoptosis in the presence of gefitinib or erlotinib. 

 

We offer EL-014, a BaF3 stable cell line expressing both EGFR (E19del) and T790M. The EGFR exon 19 mutation is an 11-18 bp in-frame deletion around the ATP-binding site encoded in exon 19 of the EGFR gene, observed in ~15-20% of lung cancer patients. The EGFR T790M mutation arises from the nucleotide change c.2369C>T in exon 20, resulting in an amino acid substitution of the threonine (T) at position 790 by a methionine (M). This cell line can be used to study the molecular mechanism underlying susceptibility of tumors to the drugs (i.e. gefitinib and erlotinib) as well as screening and validating new TKIs. 

 

Data

 

Dose-dependent growth inhibition of BaF3 cells harboring EGFR Del19 (EL-011), EGFR Ins19 (EL-009) and representative Erlotinib resistant cell line, EGFR Del19-T790M (EL-014). The cells were treated with the indicated dose of erlotinib for 24 hours and cells viability was measured using Signosis CVC reagent. EGFR Del19 stably expressing BaF3 cells (EL-011) remains 14-fold more sensitive to TKI erlotinib (IC50=0.34) than its resistance derivative EGFR Del19-T790M stably expressing BaF3 cells (EL-014) (IC50=4.9).

 

Literature

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 Citations

 

NRF2/ARE Luciferase Reporter MCF7 Stable Cell Line  SL-0010

Withaferin A induces Nrf2-dependent protection against liver injury: role of Keap1-independent mechanisms. DL Palliyaguru, DV Chartoumpekis, N Wakabayashi. Free Radical Biology and Medicine 2016. http://dx.doi.org/10.1016/j.freeradbiomed.2016.10.003

Luciferase Stable Expressing Hela Cell Line SL-0102

Redox-responsive, reversibly-crosslinked thiolated cationic helical polypeptides for efficient siRNA encapsulation and delivery.N Zheng, Z Song, Y Liu, R Zhang, R Zhang, C Yao. Journal of Controlled Release.Volume 205, 10 May 2015, Pages 231–239

Targeted delivery of cisplatin to tumor xenografts via the nanoparticle component of nano-diamino-tetrac. Thangirala Sudha, Dhruba J Bharali, Murat Yalcin, Noureldien HE Darwish, Melis Debreli Coskun, Kelly A Keating, Hung-Yun Lin, Paul J Davis, Shaker A Mousa. February 2017 ,Vol. 12, No. 3, Pages 195-205 , DOI 10.2217/nnm-2016-0315.

NFkB Luciferase Reporter Stable Cell Lines  SL-0001

Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways. V Muralidharan-Chari, J Kim, A Abuawad, M Naeem.  Int. J. Mol. Sci. 2016, 17(4), 474; doi:10.3390/ijms17040474

Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 …G Vazquez-Ortiz, C Chisholm, X Xu, TJ Lahusen, C Li… - Breast Cancer Research  2014,  Jun 24;16(3):R67. doi: 10.1186/bcr3682.

NFkB Luciferase Reporter A549 Stable Cell Lines  SL-0014

Alcohol promotes migration and invasion of triple-negative breast cancer cells through activation of p38 MAPK and JNK†M Zhao, EW Howard, AB Parris, Z Guo, Q Zhao, X Yang.  Molecular Carcinogenesis, 2016, DOI: 10.1002/mc.22538

HEK293 TCF/LEF Luciferase Reporter Stable Cell Line SL-0015

Active β-catenin is regulated by the PTEN/PI3 kinase pathway: a role for protein phosphatase PP2A. Amit Persad,1,* Geetha Venkateswaran,1,* Li Hao,1 Maria E. Garcia,1 Jenny Yoon,1 Jaskiran Sidhu,1 and Sujata Persad1. Genes Cancer. 2016 Nov; 7(11-12): 368–382., doi:  10.18632/genesandcancer.128

Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of glioma cells by inactivating Wnt/β-catenin signaling. Qingxia TaoCuiying WuRuxiang XuLijun NiuJiazhen QinNing LiuPeng ZhangEmail authorChong Wang. Cell and Tissue Research, 2017, doi:10.1007/s00441-017-2678-9

BCN057 induces intestinal stem cell repair and mitigates radiation-induced intestinal injury. Payel Bhanja, Andrew Norris, Pooja Gupta-Saraf, Andrew Hoover and Subhrajit Saha. Stem Cell Research & Therapy, vol. 9, no. 1, Feb. 2018, doi:10.1186/s13287-017-0763-3.

(Nrf2/ARE) luciferase reporter cell line HEK293

Direct Antioxidant Properties of Methotrexate: Inhibition of Malondialdehyde-Acetaldehyde-Protein Adduct Formation and Superoxide Scavenging. Matthew C. Zimmermana, Dahn L. Clemensb, c, Michael J. Duryeeb, Cleofes Sarmientoa, Andrew Chioub, Carlos D. Hunterb, Jun Tiana, Lynell W. Klassenb, c, James R. O’Dellb, c, Geoffrey M. Thieleb, c, Redox Biology,2017.07.018, doi: 10.1016/j.redox.2017.07.018

Active β-catenin is regulated by the PTEN/PI3 kinase pathway: a role for protein phosphatase PP2A. Amit Persad1,*, Geetha Venkateswaran1,*, Li Hao1, Maria E. Garcia1, Jenny Yoon1, Jaskiran Sidhu1 and Sujata Persad1.Genes & Cancer. January 30, 2017 . https://doi.org/10.18632/genesandcancer.128