Abstract
We have studied the development of resistance to cisplatin in cultured KB-3-1 human cervical adenocarcinoma (HeLa) cells and BEL-7404 human hepatoma cells. In a single-step selection, it is possible to develop a pleiotropic phenotype consisting of the following: (a) cross-resistance to other platinum compounds, arsenite, cadmium, methotrexate and nucleoside analogs; (b) corresponding reduced accumulation of these agents; (c) reduced receptor-mediated and fluid phase mediated endocytosis; (d) altered cytoskeleton, including disruption of actin microfilaments, filament structures, and microtubules; (e) a defect in membrane protein trafficking consisting of relocalization to intracellular vesicles of several transmembrane proteins such as the ABBC1 transporter (MRP1, GS-X pump), glucose transporter (GluT1), and folate binding protein (FBP); and (f) altered mitochondrial morphology and function. We hypothesize that this pleiotropic phenotype reflects a basic cellular defense mechanism against cytotoxic materials that are not hydrophobic enough to enter the cell by simple diffusion, but have multiple other mechanisms of cell entry including piggybacking on existing receptors and endocytosis, and speculate that a relatively simple cellular switch can actuate this pleiotropic response.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
