Related Experiment Video

Updated: Feb 11, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells

Wei Li1,2, Ling Xu1,2, Xiaofang Che1,2

  • 1Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.

BMC Cancer
|May 4, 2018
PubMed
Abstract

Insights

Tamoxifen resistance in breast cancer can be reversed by targeting the ER-c-Src-HER2 complex. Overexpression of c-Cbl inhibits this complex, restoring tamoxifen sensitivity in HER2-positive cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tamoxifen is a primary treatment for estrogen receptor (ER)-positive breast cancer.
  • Tamoxifen resistance is a significant clinical challenge, and its mechanisms remain incompletely understood.
  • This study investigates the role of the ER-c-Src-HER2 complex in tamoxifen resistance.

Purpose of the Study:

  • To determine if the formation of the ER-c-Src-HER2 complex contributes to tamoxifen resistance in breast cancer.
  • To explore the potential of targeting this complex to overcome tamoxifen resistance.

Main Methods:

  • Cell viability and proliferation assays (MTT, colony formation).
  • Protein expression and complex detection (Western blot, immunoprecipitation, immunofluorescence).
  • Gene knockdown (siRNA), drug inhibition (PP2, trastuzumab, nystatin), and in vivo xenograft models.

Main Results:

  • Tamoxifen-resistant (BT474) and sensitive (T47D) cell lines were identified.
  • ER-c-Src-HER2 complex formation was present in resistant cells and induced in sensitive cells upon HER2 overexpression.
  • HER2 knockdown, c-Src inhibition, trastuzumab, and c-Cbl overexpression reversed tamoxifen resistance by disrupting the complex.

Conclusions:

  • The ER-c-Src-HER2 complex is implicated in tamoxifen resistance in HER2-overexpressing breast cancer.
  • c-Cbl can reverse tamoxifen resistance by inhibiting the formation of this complex.
  • Targeting the ER-c-Src-HER2 complex presents a potential therapeutic strategy.
Keywords:
Breast cancerC-CblHER2ResistanceTamoxifen

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