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Imatinib mesylate enhances the malignant behavior of human breast carcinoma cells

Germana Rappa1, Fabio Anzanello, Aurelio Lorico

  • 1Department of Drug Development, Nevada Cancer Institute, One Breakthrough Way, Las Vegas, NV 89135, USA.

Cancer Chemotherapy and Pharmacology
|July 3, 2010
PubMed
Abstract

Insights

Imatinib treatment paradoxically increased breast cancer aggressiveness in mice and cell cultures. Surviving cells showed enhanced motility and gene expression linked to malignancy, suggesting caution for clinical use.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Imatinib mesylate (Imatinib) is a tyrosine kinase inhibitor used for chronic myeloid leukemia and gastrointestinal stromal tumors.
  • Its efficacy in advanced and metastatic breast cancer is under investigation due to c-abl, c-kit, and PDGFR expression in breast cancer cells.

Purpose of the Study:

  • To investigate the effects of Imatinib on human MA-11 breast carcinoma cells.
  • To evaluate Imatinib's impact in vitro and in mouse xenografts.

Main Methods:

  • MA-11 breast carcinoma cells were treated with Imatinib in vitro and in mouse xenografts.
  • Effects on tumor growth, cell survival, motility, and gene expression were analyzed.

Main Results:

  • In vivo, Imatinib did not inhibit tumor growth but increased tumor take rate and abdominal mass formation.
  • In vitro, surviving MA-11 cells exhibited increased motility and over-expressed aggressive behavior-associated genes.
  • Differential gene expression in Wnt and MAPK pathways and increased promoter activity were observed.

Conclusions:

  • Imatinib treatment may enhance malignancy in residual breast cancer cells.
  • Caution is advised for the clinical use of Imatinib in breast cancer.
  • Identifying regulatory pathways in surviving cells could reveal therapeutic targets.

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