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Transformation by v-ras oncogene correlates with an increased drug-resistance in an epithelial thyroid-cell system

D Spalletticernia1, I Dagnano, C Salvatore

  • 1UNIV NAPLES,FAC MED & CHIRURG,DIPARTIMENTO BIOL & PATOL CELLULARE & MOLEC,CNR,I-80131 NAPLES,ITALY. CNR,IST TECNOL BIOMED,I-00161 ROME,ITALY. REGINA ELENA INST CANC RES,CTR EXPTL RES,CHEMIOTERAPIA SPERIMENTALE PRECLIN LAB,I-00158 ROME,ITALY.

International Journal of Oncology
|May 11, 2011
PubMed

Insights

Ras transformation in epithelial cells reduces anticancer drug sensitivity by altering cell membrane potential, not multidrug resistance protein levels. This finding impacts cancer drug resistance research.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Ras transformation is linked to cancer progression and altered cellular functions.
  • Investigating mechanisms of anticancer drug resistance is crucial for effective cancer therapy.

Purpose of the Study:

  • To evaluate the impact of ras transformation on anticancer drug sensitivity in an epithelial cell system.
  • To determine the correlation between ras expression, cell malignancy, and drug resistance.

Main Methods:

  • Utilized an epithelial cell system with varying ras expression levels.
  • Assessed drug accumulation and cell membrane potential using flow cytometry.
  • Correlated findings with multidrug resistance (mdr) protein expression.

Main Results:

  • Transformed cell lines exhibited diminished drug accumulation, correlating with membrane depolarization.
  • The most resistant cell line (MPTK-6) showed the lowest drug accumulation and membrane potential.
  • No correlation was found between drug resistance and the multidrug resistance (mdr) protein.

Conclusions:

  • Ras neoplastic transformation of rat thyroid epithelial cells alters cell membrane potential.
  • Modified membrane potential is a potential factor contributing to anticancer drug resistance.

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