DiGiuseppe J A, Kastan M B, Weng L J, Gore S D
Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8963, USA.
In Vivo. 1999 Jan-Feb;13(1):1-6.
Hematopoietic growth factors (HGF) can suppress chemotherapy-induced programmed cell death (apoptosis) in hematopoietic cells. Although HGF can modulate the expression of apoptosis-regulatory genes, including bcl-2, bax, and p21WAF1/CIP1 in cell lines, few data address whether HGF regulate the expression of these proteins in primary acute myeloid leukemia (AML).
We evaluated the expression of bcl-2, bax, and p21WAF1/CIP1 in primary samples from patients with AML in the presence and absence of HGF. The potential association of HGF-induced changes in the levels of these proteins with inhibition of chemotherapy-induced apoptosis was further investigated.
While a combination of steel factor (SF) and PIXY321 inhibited etoposide-induced apoptosis in 8/11 primary AML samples studied, Bcl-2 and bax protein levels were unaffected by exposure to HGF and/or etoposide. In contrast, HGF enhanced basal and etoposide-induced p21WAF1/CIP1 protein levels in 9/11 and 7/11 of the cases, respectively. In several cases, inhibition of apoptosis by HGF was seen without up-regulation of p21WAF1/CIP1 levels, suggesting that modulation of p21WAF1/CIP1 is not required for HGF-mediated inhibition of apoptosis.
These data indicate that HGF-mediated inhibition of chemotherapy-induced apoptosis in primary AML samples is not mediated through changes in Bcl-2, bax, and p21WAF1/CIP1 protein levels.
造血生长因子（HGF）可抑制化疗诱导的造血细胞程序性细胞死亡（凋亡）。尽管HGF可调节凋亡调控基因的表达，包括细胞系中的bcl-2、bax和p21WAF1/CIP1，但很少有数据探讨HGF是否调节原发性急性髓系白血病（AML）中这些蛋白的表达。
我们评估了在有或无HGF的情况下，AML患者原发性样本中bcl-2、bax和p21WAF1/CIP1的表达。进一步研究了HGF诱导的这些蛋白水平变化与化疗诱导凋亡抑制之间的潜在关联。
虽然在研究的11例原发性AML样本中有8例，钢因子（SF）和PIXY321的组合抑制了依托泊苷诱导的凋亡，但Bcl-2和bax蛋白水平不受HGF和/或依托泊苷暴露的影响。相反，HGF分别在9/11和7/11的病例中增强了基础和依托泊苷诱导的p21WAF1/CIP1蛋白水平。在一些病例中，观察到HGF抑制凋亡而p21WAF1/CIP1水平未上调，这表明HGF介导的凋亡抑制不需要p21WAF1/CIP1的调节。
这些数据表明，HGF介导的原发性AML样本中化疗诱导凋亡的抑制不是通过Bcl-2、bax和p21WAF1/CIP1蛋白水平的变化介导的。
