Tzen Chin-Yuan, Huang Yu-Wen, Wang Man-Ning
Department of Pathology, Mackay Memorial Hospital, No. 45, Min-Sheng Road, Tam-Shui, Taipei 251, Taiwan, Republic of China.
Chin J Physiol. 2007 Apr 30;50(2):57-62.
The mechanism governing cell quiescence remains to be elucidated, albeit some tumor suppressor genes are known to be involved in this process. If more genes belonging to this regulatory circuit are identified, we will have a better understanding on cell quiescence. For this purpose, the present study was designed to clone genes preferentially expressed in cell quiescence. Using the method of differential display, we cloned ras-recision gene (rrg), also known as lysyl oxidase gene (lox), from BALB/c 3T3T cells, which were rendered quiescent by serum deprivation. Northern blot analysis showed that the induction of rrg/lox gene could be detected as early as 12 h following serum deprivation and it was dramatically elevated from 24 hours on after serum starvation. Induction of rrg/lox was also observed in cells rendered quiescent by contact inhibition, indicating that rrg/lox is induced by cell quiescence in general rather than specific to serum deprivation. Because rrg/lox gene products are known to be involved in extracellular matrix maturation, and function as tumor suppressors against ras oncogene, our finding suggests that quiescence-associated cell physiology is partly mediated by induction of rrg/lox.
尽管已知一些肿瘤抑制基因参与了这一过程,但控制细胞静止的机制仍有待阐明。如果能鉴定出更多属于这一调控回路的基因,我们将对细胞静止有更深入的了解。为此,本研究旨在克隆在细胞静止期优先表达的基因。利用差异显示法,我们从经血清饥饿处理而进入静止期的BALB/c 3T3细胞中克隆了ras-切割基因(rrg),该基因也被称为赖氨酰氧化酶基因(lox)。Northern印迹分析表明,血清饥饿后12小时即可检测到rrg/lox基因的诱导表达,且血清饥饿24小时后其表达显著升高。在因接触抑制而进入静止期的细胞中也观察到了rrg/lox的诱导表达,这表明rrg/lox通常是由细胞静止诱导产生的,而非血清饥饿所特有的。由于已知rrg/lox基因产物参与细胞外基质成熟,并作为针对ras癌基因的肿瘤抑制因子发挥作用,我们的研究结果表明,与静止相关的细胞生理过程部分是由rrg/lox的诱导介导的。