Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4.
Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4.
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人类细胞无限分裂的遗传分析：人类 4 号染色体上存在细胞衰老相关基因的证据。
DOI：
10.1073/pnas.88.13.5635
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发表时间：
1991
影响因子：
11.1
通讯作者：
Pereira-Smith,OM
中科院分区：
文献类型：
--
作者：
Ning,Y;Weber,JL;Killary,AM;Ledbetter,DH;Smith,JR;Pereira-Smith,OM
早期的研究表明，正常细胞与永生人类细胞的融合产生了具有有限分裂潜力的杂交体。这表明有限增殖（细胞衰老）的表型是显性的，而永生细胞是由正常生长调节基因的隐性变化引起的。在另外的研究中，我们利用了永生表型是隐性的这一事实，并通过将各种永生人类细胞系彼此融合，确定了四个互补组用于无限期分裂。将细胞系分配到特定的群体使我们能够采取集中的方法来识别在永生细胞中被修饰的参与生长调节的染色体和基因。我们在这里报告，一个正常的人类4号染色体导入三个永生细胞系（HeLa，J82，T98 G）分配到互补组B导致增殖损失和永生表型逆转。未观察到对代表其他互补组的细胞系的增殖潜力的影响。这一结果表明，参与细胞衰老和正常生长调节的基因位于4号染色体上。
Earlier studies had demonstrated that fusion of normal with immortal human cells yielded hybrids having limited division potential. This indicated that the phenotype of limited proliferation (cellular senescence) is dominant and that immortal cells result from recessive changes in normal growth-regulatory genes. In additional studies, we exploited the fact that the immortal phenotype is recessive and, by fusing various immortal human cell lines with each other, identified four complementation groups for indefinite division. Assignment of cell lines to specific groups allowed us to take a focused approach to identify the chromosomes and genes involved in growth regulation that have been modified in immortal cells. We report here that introduction of a normal human chromosome 4 into three immortal cell lines (HeLa, J82, T98G) assigned to complementation group B resulted in loss of proliferation and reversal of the immortal phenotype. No effect on the proliferation potential of cell lines representative of the other complementation groups was observed. This result suggests that a gene(s) involved in cellular senescence and normal growth regulation resides on chromosome 4.