TY - JOUR
T1 - DNA amplification in multidrug, cross-resistant Chinese hamster ovary cells
T2 - Molecular characterization and cytogenetic localization of the amplified DNA
AU - Teeter, L. D.
AU - Atsumi, S. I.
AU - Sen, S.
AU - Kuo, T.
PY - 1986
Y1 - 1986
N2 - Vincristine-resistant (VCR) Chinese hamster ovary (CHO) cells have been established by stepwise selection in increasing concentrations of vincristine. These cells exhibit multidrug cross-resistance to a number of drugs that have no structural or functional similarities. Cytogenetic analyses of resistant cells revealed the presence of double minutes and expanded chromosomal segments, thus implicating gene amplification as a possible mechanisms of resistance. An amplified DNA segment isolated from other multidrug cross-resistant CHO cell lines is also amplified in our VCR lines. This DNA segment was used as a probe to screen a cosmid library of VCR genomic DNA, and overlapping clones were retrieved. All of these segments, totaling ~45 kilobases (kb), were amplified in VCR cells. Using in situ hybridization, we localized the amplification domain to the long arm of CHO chromosome 1 or Z1. Northern hybridization analysis revealed that a 4.3-kb mRNA was encoded by this amplified DNA domain and was over-produced in the VCR cells. Suggestions for the involvement of these amplified DNA segments in the acquisition of multidrug cross-resistance in animal cells are also presented.
AB - Vincristine-resistant (VCR) Chinese hamster ovary (CHO) cells have been established by stepwise selection in increasing concentrations of vincristine. These cells exhibit multidrug cross-resistance to a number of drugs that have no structural or functional similarities. Cytogenetic analyses of resistant cells revealed the presence of double minutes and expanded chromosomal segments, thus implicating gene amplification as a possible mechanisms of resistance. An amplified DNA segment isolated from other multidrug cross-resistant CHO cell lines is also amplified in our VCR lines. This DNA segment was used as a probe to screen a cosmid library of VCR genomic DNA, and overlapping clones were retrieved. All of these segments, totaling ~45 kilobases (kb), were amplified in VCR cells. Using in situ hybridization, we localized the amplification domain to the long arm of CHO chromosome 1 or Z1. Northern hybridization analysis revealed that a 4.3-kb mRNA was encoded by this amplified DNA domain and was over-produced in the VCR cells. Suggestions for the involvement of these amplified DNA segments in the acquisition of multidrug cross-resistance in animal cells are also presented.
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U2 - 10.1083/jcb.103.4.1159
DO - 10.1083/jcb.103.4.1159
M3 - Article
C2 - 3771630
AN - SCOPUS:0022967025
SN - 0021-9525
VL - 103
SP - 1159
EP - 1166
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -