Reddy D E, Sandhu A K, DeRiel J K, Athwal R S, Kaur G P
Fels Institute for Cancer Research, 3307 North Broad Street, AHB Room 201, Temple University School of Medicine, Philadelphia, Pennsylvania, PA 19140, USA.
Oncogene. 1999 Sep 9;18(36):5100-017. doi: 10.1038/sj.onc.1202888.
We have mapped a cellular senescence gene, SEN16, within a genetic distance of 3 - 7 cM, at 16q24.3. Microcell mediated transfer of a normal human chromosome 16, 16q22-qter or 16q23-qter restored cellular senescence in four immortal cell lines, derived from human and rat mammary tumors. The resumption of indefinite cell proliferation, concordant with the segregation of the donor chromosome, confirmed the presence of a senescence gene at 16q23-qter. While microcell hybrids were maintained in selection medium to retain the donor chromosome, sporadic immortal revertant clones arose among senescent cells. Reversion to immortal growth could occur due to inactivation of the senescence gene either by a mutation or a deletion. The analysis for chromosome 16 specific DNA markers, in revertant clones of senescent microcell hybrids, revealed a consensus deletion, spanning a genetic interval of approximately 3 - 7 cM at 16q24.3.
我们已将一个细胞衰老基因SEN16定位在16q24.3处，遗传距离为3 - 7厘摩。微细胞介导的正常人16号染色体、16q22 - qter或16q23 - qter的转移，恢复了源自人及大鼠乳腺肿瘤的4种永生细胞系的细胞衰老。与供体染色体分离一致的无限细胞增殖的恢复，证实了16q23 - qter处存在一个衰老基因。当微细胞杂种在选择培养基中维持以保留供体染色体时，衰老细胞中出现了散发性的永生回复克隆。回复到永生生长可能是由于衰老基因通过突变或缺失而失活。对衰老微细胞杂种的回复克隆中16号染色体特异性DNA标记的分析，揭示了一个共有的缺失，跨越16q24.3处约3 - 7厘摩的遗传区间。
