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Drug resistance in Chinese hamster lung and mouse tumor cells
Abstract:
Studies of Chinese hamster and mouse cells with high levels of acquired resistance to dactinomycin, daunorubicin, or vincristine have shown that these different permeability mutants all display similar phenotypic alterations: dramatic changes toward normal cell morphology and growth behavior and substantially reduced oncogenic potential. All three resistant cell types show increased expression of a high molecular weight plasma membrane glycoprotein species, gp150. Uniquely, vincristine-resistant cells contain gene amplification-associated chromosome abnormalities (homogeneously staining regions or double minute chromosomes), and they oversynthesize a low molecular weight cytosolic protein (V19). Cells grown in the absence of drug are phenotypically unstable. Revertant cells decline in resistance, length or number of homogeneously staining regions or double minute chromosomes, and expression of gp150 and V19. These proteins are thus candidate products of amplified genes which may or may not be manifested cytogenetically. The phenomena of drug resistance and reverse transformation are currently being addressed in protein phosphorylation studies.
Insights
Acquired drug resistance in cells leads to normal morphology and reduced cancer potential. These changes involve specific protein expressions, with vincristine resistance uniquely showing gene amplification.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Acquired multidrug resistance (MDR) is a significant challenge in cancer therapy.
- Previous studies indicated altered cellular phenotypes in drug-resistant cells.
Purpose of the Study:
- To investigate the phenotypic and molecular changes associated with acquired resistance to dactinomycin, daunorubicin, and vincristine in mammalian cells.
- To identify potential molecular markers associated with drug resistance and reverse transformation.
Main Methods:
- Comparative analysis of drug-resistant Chinese hamster and mouse cell lines.
- Phenotypic characterization including cell morphology, growth rate, and oncogenic potential.
- Molecular analysis including protein expression (gp150, V19) and cytogenetic evaluation (gene amplification).
Main Results:
- Drug-resistant cells exhibited normalization of morphology and growth, with reduced oncogenic potential.
- Increased expression of a high molecular weight glycoprotein (gp150) was observed in all resistant cell types.
- Vincristine-resistant cells uniquely displayed gene amplification and overexpressed a low molecular weight protein (V19).
- Phenotypic instability was noted in cells grown without drug, with revertants losing resistance and associated molecular markers.
Conclusions:
- Acquired drug resistance induces significant cellular changes, including reverse transformation.
- gp150 and V19 are candidate products of amplified genes, potentially linked to drug resistance and altered cell behavior.
- Further investigation into protein phosphorylation is warranted to understand the mechanisms of drug resistance and reverse transformation.