Effect of O-GlcNAcylation on tamoxifen sensitivity in breast cancer derived MCF-7 cells
type: Dataset
description: One of the hallmarks of cancer cells is to exhibit increased uptake and consumption of glucose.3-5% of the glucose entering into the cell leads to a minor pathway of the glucose metabolismknown as the hexosamine biosynthetic pathway (HBP). UDP-N-acetylglucosamine is the endproduct of HBP and is used as substrate by OGT (O-GlcNAc transferase) to modify diverserange of nuclear and cytoplasmic proteins with a recently characterized post-translationalmodification called O-GlcNAcylation. It corresponds to the addition of sugar moiety O-linked β-N-acetylglucosamine (O-GlcNAc) on serine or threonine residue of proteins. This process isantagonized by another enzyme called O-GlcNAcase (OGA). Recent studies indicated thepresence of increased O-GlcNAcylation level in several cancer cells. Moreover, inhibition ofOGT has been shown to reduce in vivo and in vitro tumor growth of breast cancer cells.However, the relationship between O-GlcNAcylation and the response to anti-cancer therapy hasnot been studied. Tamoxifen is the oldest and most prescribed selective-estrogen receptormodulator (SERM) for patients with estrogen receptor (ER)-positive breast cancer. Tamoxifen isknown to reduce tumor growth and invasion. Despite its beneficial effects de novo and acquiredresistance are great obstacles in its clinical effectiveness. We found that O-GlcNAc elevation inMCF-7 cells protected them from tamoxifen-induced cell death. Increased O-GlcNAc alsoincreased PI3-K/Akt signaling. However, the protective effect of PUGNAc+glucosamine fromtamoxifen-induced cell death is independent of PI3K/Akt pathway. Increased O-GlcNAcylationalso led to reduced ESR1 promoter activity and decreased expression of ERα at mRNA andprotein levels. The decrease in ERα expression is correlated with a reduced expression of twotamoxifen regulated genes i.e. early growth response 1 and p21 Waf1/Cip1. In conclusion, thisstudy showed for the first time the involvement of O-GlcNAcylation in reducing tamoxifen142sensitivi…
identifier: NNT: 2013PA05T006
issued: 2026-05-08T00:20:40.322411
language: en
modified: 2026-05-08T00:20:40.322415
contact point: Organization
  fn: CCSD
keyword: cancer-du-sein
keyword: infoeu-reposemanticsdoctoralthesis
keyword: o-glcnacylation
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: theses
landing page: https://theses.hal.science/tel-00912341

Effect of O-GlcNAcylation on tamoxifen sensitivity in breast cancer derived MCF-7 cells
type: Distribution
format: HTML
issued: 2026-05-08T00:20:40.323968
modified: 2026-05-08T00:20:40.315038
access URL: https://theses.hal.science/tel-00912341

test_moissonnage_selune
type: Agent