Quantitative correlation of homogeneously stained regions on chromosome 10 with dihydrofolate reductase enzyme in human cells.
Quantitative correlation of homogeneously stained regions on chromosome 10 with dihydrofolate reductase enzyme in human cells.
复制标题
人类细胞中 10 号染色体上均匀染色区域与二氢叶酸还原酶的定量相关性。
DOI：
10.1073/pnas.80.3.807
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发表时间：
1983
影响因子：
11.1
通讯作者：
Cheng,YC
中科院分区：
文献类型：
--
作者：
Wolman,SR;Craven,ML;Grill,SP;Domin,BA;Cheng,YC
基因扩增可以在染色体内被可视化为均匀染色区域（HSR），并且HSR很少在人类肿瘤细胞中被报道为具有扩增基因的鉴定。从对甲氨蝶呤（MTX）具有抗性的KB细胞衍生的亲本系和7个克隆含有二氢叶酸还原酶（DHFR;四氢叶酸脱氢酶; EC 1.5.1.3），范围从亲本中的0.007单位/mg到克隆7A中的0.369单位/mg，对MTX的抗性增加了13，000倍。这种酶与其他人类来源的DHFR相同，包括白血病患者的DHFR。定位于染色体10的长臂（q26）的HSR存在于在2.5 μ M MTX或以上选择的克隆中。每个细胞10 q数量的增加、HSR数量的增加和DHFR数量的增加具有良好的相关性。即使在没有MTX选择的情况下，染色体变化也随时间稳定，酶的产生也是如此。没有克隆显示双分钟。基因拷贝数低。在大HSR存在下的稳定性和低基因拷贝与针对鼠肿瘤描述的模式不同。DHFR的人类基因可能与10号染色体的长臂有关。
Gene amplification may be visualized within a chromosome as a homogeneously stained region (HSR) and HSRs have rarely been reported in human tumor cells with identification of the amplified gene. A parental line and seven clones derived from KB cells resistant to methotrexate (MTX) contain dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; EC 1.5.1.3), ranging from 0.007 unit/mg in the parent to 0.369 unit/mg in clone 7A with a 13,000-fold increase in resistance to MTX. The enzyme is identical to DHFR from other human sources, including that from leukemic patients. A HSR localized to the long arm of chromosome 10(q26) is present in clones selected at or above 2.5 microM MTX. Increase in number of 10q per cell, increase in number of HSR, and increasing amounts of DHFR correlate well. The chromosome change is stable with time as is enzyme production even in the absence of selection by MTX. No clone has shown double minutes. The gene copy number is low. The stability and low gene copy in the presence of large HSRs differ from the pattern described for murine tumors. A human gene for DHFR may be associated with the long arm of chromosome 10.