Abstract
Background: Triple Negative Breast Cancer (TNBC) commonly displays Epidermal growth factor receptor (EGFR). Effective EGFR degradation results in the suppression of tumor in various models. Studies have addressed the relevance of this strategy in the treatment of TNBC. In the present study, we examined the effect of 17 β- estradiol on EGFR expression in MDA-MB-231 (TNBC) cell line and assessed whether 17 β-estradiol degrades EGFR by ubiquitination pathway.
Objectives: The objective of this study is to treat MDA-MB-231 cell lines with Cycloheximide with or without 17β-estrdiol to observe whether 17β-estradiol leads to EGFR degradation and to treat with MG-132 to assess whether degradation occurs through ubiquitination pathway.
Methods: MDA-MB-231 cells were treated with 17β-estradiol (E2) and EGFR expression was studied by western blotting at different intervals by using Cycloheximide chase. To assess ubiquitination pathway of degradation of EGFR in MDA-MB-231 cell line, MG-132 was used.
Results: EGFR expression was reduced with β-estradiol treatment in MDA-MB-231 cell line with Cycloheximide chase. Upon Treatment with MG-132 and E2, EGFR expression did not reduce, suggesting that Estrogen degrades EGFR by ubiquitination pathway.
Conclusion: Estrogen degrades EGFR in MDA-MB-231 cells and this degradation occurs by ubiquitination.
Keywords: Triple negative breast cancer, MDA-MB-231, estrogen, epidermal growth factor receptor, MG-132, ubiquitination.
[http://dx.doi.org/10.1056/NEJMra1001389] [PMID: 21067385]
[http://dx.doi.org/10.1002/cncr.22836] [PMID: 17620276]
[http://dx.doi.org/10.1007/BF01809293] [PMID: 2176111]
[http://dx.doi.org/10.1126/science.2470152] [PMID: 2470152]
[http://dx.doi.org/10.1002/cncr.24816] [PMID: 20082448]
[http://dx.doi.org/10.1007/s11154-007-9033-5] [PMID: 17486454]
[http://dx.doi.org/10.3322/caac.21320] [PMID: 26513636]
[http://dx.doi.org/10.1016/S1470-2045(14)70364-X] [PMID: 25456381]
[http://dx.doi.org/10.1073/pnas.0913476107] [PMID: 20616078]
[http://dx.doi.org/10.1083/jcb.201001008] [PMID: 20513767]
[http://dx.doi.org/10.1074/jbc.M115.663559] [PMID: 26055716]
[http://dx.doi.org/10.1007/978-1-61779-474-2_36] [PMID: 22350909]
[http://dx.doi.org/10.1038/onc.2013.279] [PMID: 23851495]
[http://dx.doi.org/10.1083/jcb.125.2.299] [PMID: 8163547]
[http://dx.doi.org/10.1016/0092-8674(90)90481-S] [PMID: 2111732]
[http://dx.doi.org/10.1128/MCB.23.24.9251-9261.2003] [PMID: 14645527]
[http://dx.doi.org/10.1152/physrev.00027.2001] [PMID: 11917093]
[http://dx.doi.org/10.1038/sj.cdd.4401702] [PMID: 16094395]
[http://dx.doi.org/10.1038/nrm2468] [PMID: 18698327]
[http://dx.doi.org/10.1016/j.tibs.2010.05.005] [PMID: 20541423]
[http://dx.doi.org/10.1016/S0021-9258(20)82050-X] [PMID: 6305978]
[http://dx.doi.org/10.1016/j.bbamcr.2013.05.026] [PMID: 23747565]
[http://dx.doi.org/10.1146/annurev.biochem.78.081507.101607] [PMID: 19489727]
[http://dx.doi.org/10.1038/nature10774] [PMID: 22237024]
[http://dx.doi.org/10.1002/pros.20640] [PMID: 17705178]
[http://dx.doi.org/10.1002/cncr.25862] [PMID: 21656753]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1373] [PMID: 17699844]
[http://dx.doi.org/10.1210/er.2007-0022] [PMID: 17916740]
[http://dx.doi.org/10.1093/annonc/mdt132] [PMID: 23579816]
[http://dx.doi.org/10.2174/1566524018666181109121849] [PMID: 30411685]
[http://dx.doi.org/10.1186/bcr3358] [PMID: 23158001]
[http://dx.doi.org/10.1074/jbc.274.32.22151] [PMID: 10428778]
[http://dx.doi.org/10.1091/mbc.e02-08-0532] [PMID: 12631709]
[http://dx.doi.org/10.1083/jcb.150.4.905] [PMID: 10953014]
[http://dx.doi.org/10.2174/156652411794859269] [PMID: 21342128]
[http://dx.doi.org/10.1073/pnas.0932599100] [PMID: 12802020]
[http://dx.doi.org/10.1083/jcb.200302131] [PMID: 12900395]
[PMID: 9815883]
[PMID: 1627426]
[http://dx.doi.org/10.2174/1566524018666180416101522] [PMID: 29663884]
[http://dx.doi.org/10.3109/10409239709082573] [PMID: 9239493]
[http://dx.doi.org/10.1002/path.2004] [PMID: 16739104]
[http://dx.doi.org/10.1186/1471-2164-8-258] [PMID: 17663798]
[http://dx.doi.org/10.1097/PPO.0b013e3181d24fc1] [PMID: 20164687]