Increased frequency of P-glycoprotein gene amplification in colchicine-resistant Rat-1 clones transformed by v-src.
A rat fibroblast cell line (Rat-1) carrying a temperature-sensitive mutation of v-src was used to determine whether inducible cellular transformation altered the ability of cells to amplify the p-glycoprotein gene in response to colchicine selection. Transformed and nontransformed Rat-1 fibroblasts selected under 4 times the LD50 generated the same number of colchicine-resistant colonies. We next examined colchicine-resistant colonies derived from transformed cells and compared them to colchicine-resistant colonies derived from nontransformed cells. When Rat-1 cells were selected at 35 degrees C (transforming temperature), 7 out of 7 clones exhibited a 3- to 5-fold p-glycoprotein gene amplification. These results contrasted to those found at the nontransforming temperature (40 degrees C); none of the 8 colchicine-resistant clones examined had amplified the p-glycoprotein gene. Thus in Rat-1 cells carrying a temperature-sensitive v-src gene, p-glycoprotein gene amplification was observed at a high frequency only in transformed clones selected at the temperature permissive for v-src activity.
Lin
T
T
National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland, USA.
Trent
J M
JM
Milliken
D
D
Shimm
D S
DS
Donaldson
R
R
Hill
A B
AB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D003078:Colchicine / Q000494:pharmacology; D004279:DNA, Viral / Q000032:analysis; D004351:Drug Resistance; D005784:Gene Amplification; D015967:Gene Expression Regulation, Viral; D016391:Genes, src; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics; D051381:Rats
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004279:DNA, Viral; D012367:RNA, Viral; D015688:Oncogene Protein pp60(v-src); D003078:Colchicine