Intracellular expression of P-glycoprotein in a human colon tumor cell line.

A number of human tumor cell lines originating in tissues which normally express high levels of P-glycoprotein were examined for the expression of mdr-1 RNA and P-glycoprotein and their sensitivity to doxorubicin and vincristine. There was a wide variation in expression levels and in drug sensitivity among the cell lines. In the human colon tumor cell line, LS 174T, high levels of P-glycoprotein and mdr-1 RNA were observed, but this line was very sensitive to doxorubicin and vincristine. Immunoprecipitation of P-glycoprotein from preparations of membrane and cytoplasmic proteins and immunofluorescence studies using anti-P-glycoprotein antibodies revealed that P-glycoprotein in these cells is not associated with the plasma membrane, but is, instead, found intracellularly. These results emphasize the need for functional analysis of P-glycoprotein in cells that express this mediator of multidrug resistance.