Spontaneous multidrug transport in human glioma cells is regulated by transforming growth factors type ?

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Abstract
The multidrug transporting cell membrane molecule P-glycoprotein can be spontaneously expressed in human glioma cells. Transcripts of mdr genes were detected in glial tumor cells by polymerase chain reaction and Northern blotting, expression of P-glycoprotein was analyzed by immunocytochemistry and functional activity by cytofluorometry of fluorescent probe transport. In vitro treatment of glioma cells with vincristine induced coordinate over-expression of both mdr1 and mdr3 genes associated with very high P-glycoprotein-mediated multidrug transport, resistant to the inhibitory activity of chemosensitizers like verapamil. The physiological modulators of multidrug transport are as yet unknown. We therefore initiated a screening program to analyze the effects of cytokines on multidrug transport. We observed, that transforming growth factors β1, -β2, and β1.2-but not the related bone morphogenetic protein (BMP) 2-inhibited multidrug transport. Interestingly, BMP 2 antagonized the TGF-β induced inhibition of multidrug transport.