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Updated: May 13, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

The EGR1/caspase-14/HIF-1α axis mediates tamoxifen resistance in MCF-7 breast cancer cells

Feihu Ji1, Anping Zhao2, Qiuxu Chen1

  • 1Department of Clinical Laboratory, The People's Hospital of Yubei District of Chongqing, Chongqing, 401120, China.

Open Life Sciences
|May 12, 2026
PubMed

Insights

Caspase14 promotes tamoxifen resistance in breast cancer by regulating the EGR1/HIF-1α pathway. Targeting Caspase14 may overcome resistance to endocrine therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Tamoxifen resistance is a major challenge in breast cancer treatment.
  • The role of Caspase14 in tamoxifen resistance via the EGR1/HIF-1α axis is not well understood.

Purpose of the Study:

  • To investigate how Caspase14 regulates the early growth response protein 1 (EGR1)/hypoxia-inducible factor 1-alpha (HIF-1α) axis to promote 4-hydroxytamoxifen (4-OHT) resistance in MCF7 breast cancer cells.

Main Methods:

  • Utilized cell-based genetic and biochemical assays including small-interference RNA knockdown, plasmid overexpression, Western blotting, qPCR, IC50 assays, and Chromatin immunoprecipitation.
  • Compared Caspase14 expression and activity in tamoxifen-sensitive versus resistant MCF7 cells.

Main Results:

  • Caspase14 expression significantly correlated with increased tamoxifen resistance (IC50 increased from 0.178 µM to 1.575 µM).
  • EGR1 knockdown decreased Caspase14 and its downstream targets (GLUT3, BCRP), identifying EGR1 as a key mediator.
  • Resistant cells showed elevated HIF-1α, promoting enhanced metabolism and migration.

Conclusions:

  • Caspase14 drives tamoxifen resistance in MCF7 cells by activating the EGR1/HIF-1α pathway, leading to increased survival, proliferation, and metabolic reprogramming.
  • Caspase14 is a potential therapeutic target to overcome tamoxifen resistance in breast cancer, with possible translational applications.
Keywords:
EGR1/HIF-1α axisHIF-1αbreast cancercaspase14tamoxifen resistance

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