Spontaneous multidrug transport in human glioma cells is regulated by transforming growth factors type beta.
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 (TGF)-beta 1, -beta 2, and -beta 1.2-but not the related bone morphogenetic protein (BMP) 2--inhibited multidrug transport. Interestingly, BMP 2 antagonized the TGF-beta induced inhibition of multidrug transport.
Abteilung für Neurologie, Universität Würzburg, Federal Republic of Germany.
H J
HJ
Schluesener
R
R
Meyermann
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008875:Middle Aged; D009423:Nervous System Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D004364:Pharmaceutical Preparations; D016212:Transforming Growth Factor beta