Kim H R, Upadhyay S, Li G, Palmer K C, Deuel T F
Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9500-4. doi: 10.1073/pnas.92.21.9500.
The platelet-derived growth factor (PDGF) is a potent mitogen for murine fibroblasts. PDGF-stimulated cells express a set of immediate-early-response genes but require additional (progression) factors in serum to progress through the cell cycle. Serum-deprived cells are reversibly arrested in G0 phase and fail to fully traverse the G1 phase of the cell cycle when stimulated by PDGF alone. We now report that serum-deprived normal rat kidney fibroblast (NRK) cells stimulated by either PDGF AA or PDGF BB homodimers undergo apoptotic cell death. Furthermore, we show that epidermal growth factor also induces apoptotic cell death in serum-deprived NRK cells, epidermal growth factor enhances the rate of apoptosis in PDGF-treated cells, and a progression factor (insulin) but not endogenously expressed Bc1-2 fully protects NRK cells from PDGF-stimulated apoptosis. The results indicate that PDGF induces apoptosis in growth-arrested NRK cells and that the inability of NRK cells to transit the G1/S checkpoint is the critical determinant in establishing the genetic program(s) to direct the PDGF signal to apoptosis. The results suggest that polypeptide growth factors in vivo may signal cell fate positively or negatively in settings that limit the potential of cells to completely transit the cell cycle.
血小板衍生生长因子（PDGF）是一种对鼠成纤维细胞有强大作用的促有丝分裂原。PDGF刺激的细胞表达一组即刻早期反应基因，但需要血清中的其他（进展）因子才能顺利通过细胞周期。血清饥饿的细胞可逆性地停滞在G0期，当仅用PDGF刺激时，无法完全穿越细胞周期的G1期。我们现在报告，血清饥饿的正常大鼠肾成纤维细胞（NRK）受到PDGF AA或PDGF BB同型二聚体刺激后会发生凋亡性细胞死亡。此外，我们表明表皮生长因子也会在血清饥饿的NRK细胞中诱导凋亡性细胞死亡，表皮生长因子会提高PDGF处理细胞的凋亡率，一种进展因子（胰岛素）而非内源性表达的Bc1-2能完全保护NRK细胞免受PDGF刺激的凋亡。结果表明，PDGF在生长停滞的NRK细胞中诱导凋亡，而NRK细胞无法通过G1/S检查点是将PDGF信号导向凋亡的遗传程序建立的关键决定因素。结果表明，体内的多肽生长因子在限制细胞完全穿越细胞周期潜力的情况下，可能对细胞命运产生正向或负向信号作用。
