Multiple mechanisms of N-phosphonacetyl-L-aspartate resistance in human cell lines: carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged.
Multiple mechanisms of N-phosphonacetyl-L-aspartate resistance in human cell lines: carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged.
复制标题
人类细胞系中 N-膦酰基-L-天冬氨酸抗性的多种机制：氨甲酰-P 合成酶/天冬氨酸转氨甲酰酶/二氢乳清酶基因扩增仅在 2 号染色体重排时频繁出现。
DOI：
10.1073/pnas.94.5.1816
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发表时间：
1997
影响因子：
11.1
通讯作者：
Stark,GR
中科院分区：
文献类型：
--
作者：
Smith,KA;Chernova,OB;Groves,RP;Stark,MB;Martínez,JL;Davidson,JN;Trent,JM;Patterson,TE;Agarwal,A;Duncan,P;Agarwal,ML;Stark,GR
Rodent cells resistant toN-phosphonacetyl-l-aspartate (PALA) invariably contain amplified carbamyl-Psynthetase/aspartate transcarbamylase/dihydro-orotase (CAD) genes, usually in widely spaced tandem arrays present as extensions of the same chromosome arm that carries a single copy of CAD in normal cells. In contrast, amplification of CAD is very infrequent in several human tumor cell lines. Cell lines with minimal chromosomal rearrangement and with unrearranged copies of chromosome 2 rarely develop intrachromosomal amplifications of CAD. These cells frequently become resistant to PALA through a mechanism that increases the aspartate transcarbamylase activity with no increase in CAD copy number, or they obtain one extra copy of CAD by forming an isochromosome 2p or by retaining an extra copy of chromosome 2. In cells with multiple chromosomal aberrations and rearranged copies of chromosome 2, amplification of CAD as tandem arrays from rearranged chromosomes is the most frequent mechanism of PALA resistance. All of these different mechanisms of PALA resistance are blocked in normal human fibroblasts.
