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

The effects exerted by ms transformation upon sensitivity to anticancer drugs by using an epithelial cell system displaying different levels of ras expression which well correlate with different degrees of cell malignancy have been evaluated. The diminished drug accumulation of the transformed cell lines was found to be correlated with a depolarization of the cell membrane as observed by a flow cytometric analysis and not correlated with the multidrug resistance (mdr) protein. The most resistant cell line, MPTK-6, showed the lowest drug accumulation levels and the lowest membrane potential. These observations indicate that ras neoplastic transformation of the rat thyroid epithelial cells modifies the membrane potential and this modification is possibly involved in anticancer drugs resistance.