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Selective cytotoxic effect of tamoxifen on epithelial and fibroblastic cells transformed by different oncogenes

R Sanchezprieto1, J Vargas, A Durantez

  • 1CLIN PUERTA HIERRO,DEPT PATHOL,E-28035 MADRID,SPAIN. CLIN PUERTA HIERRO,DEPT INTERNAL MED,E-28035 MADRID,SPAIN.

Oncology Reports
|May 21, 2011
PubMed

Insights

Oncogenes significantly influence tamoxifen

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Tamoxifen is a widely used endocrine therapy for estrogen receptor-positive breast cancer.
  • The efficacy of tamoxifen in estrogen-negative (ER) cells is not well understood.
  • Oncogenic alterations are known to drive cancer progression and influence drug response.

Purpose of the Study:

  • To investigate the correlation between specific oncogenes and tamoxifen's cytotoxic effects in ER cells.
  • To determine how oncogene expression impacts tamoxifen sensitivity in different cell types.

Main Methods:

  • Mouse keratinocyte and fibroblastic cell lines were transformed with various oncogenes.
  • Cell viability, thymidine incorporation, and protein kinase C (PKC) levels were assessed.
  • The impact of oncogene transformation on tamoxifen sensitivity was evaluated.

Main Results:

  • v-myc and v-H-ras oncogenes enhanced tamoxifen sensitivity in both epithelial and fibroblastic cells.
  • Neu and mutant p53 oncogenes also increased tamoxifen sensitivity, particularly in epithelial cells.
  • Adenovirus E1a oncogene transformation led to tamoxifen resistance in both cell types.

Conclusions:

  • Oncogenic alterations play a crucial role in modulating tamoxifen's cytotoxic effects.
  • Tamoxifen's effectiveness may vary in malignant cells based on their specific oncogenic profile.
  • These findings suggest potential for personalized tamoxifen therapy based on cellular oncogenic status.

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