Clement A, Steele M, Brody J S, Riedel N
Department of Medicine, Boston University School of Medicine, MA 02118.
Am Rev Respir Dis. 1990 Dec;142(6 Pt 2):S60-2. doi: 10.1164/ajrccm/142.6_Pt_2.S60.
Our laboratory is studying mechanisms of growth control in alveolar type 2 cells. This highly differentiated cell is induced to proliferate in lungs of animals of all ages during various forms of growth and during the repair process after lung injury. Using type 2 (T2) cells isolated from adult and neonatal rat lungs and an SV40-T transfected T2 cell line, we have shown tha growth-arrested T2 cells constitutively express genes associated with G1 and S phase of the cell cycle, yet they do not efficiently translate the proteins encoded by these genes. This block of growth-related gene expression is post-transcriptional and appears to involve mechanisms that control translation, perhaps at the level of initiation. Furthermore, growth-arrested T2 cells initiate DNA synthesis; however, the cells do not complete the cell cycle, suggesting that they are arrested in a late stage, perhaps the G1/S border. Differential screening of a cDNA library of growth-arrested T2 cells with DNA from growing and growth-arrested T2 cells has identified four families of genes preferentially expressed in the growth-arrested cells. These genes, which are in the process of being characterized, may be responsible for the unusual type of growth arrest demonstrated by T2 cells.
我们的实验室正在研究肺泡Ⅱ型细胞的生长控制机制。这种高度分化的细胞在各种生长形式以及肺损伤后的修复过程中,会被诱导在所有年龄段动物的肺中增殖。利用从成年和新生大鼠肺中分离出的Ⅱ型(T2)细胞以及一种SV40 - T转染的T2细胞系,我们已经表明,生长停滞的T2细胞组成性地表达与细胞周期G1期和S期相关的基因,但它们不能有效地翻译这些基因所编码的蛋白质。这种与生长相关基因表达的阻断是转录后水平的,似乎涉及控制翻译的机制,可能是在起始水平。此外,生长停滞的T2细胞启动DNA合成;然而,这些细胞不能完成细胞周期,这表明它们在后期被阻滞,可能是在G1/S边界。用生长和生长停滞的T2细胞的DNA对生长停滞的T2细胞的cDNA文库进行差异筛选,已经鉴定出四个在生长停滞细胞中优先表达的基因家族。这些正在被表征的基因,可能是T2细胞所表现出的这种不寻常的生长停滞类型的原因。