Granerus M, Bierke P, Zumkeller W, Smith J, Engström W, Schofield P N
Department of Pathology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, PO Box 7028, S-75007 Uppsala, Sweden.
Clin Mol Pathol. 1995 Jun;48(3):M153-7. doi: 10.1136/mp.48.3.m153.
Aim-To study how insulin-like growth factor II (IGF-II) affects the behaviour of human teratoma cells.Methods-The human pluripotential teratoma cell line Tera 2 was cultured under serum-free conditions in the presence or absence of IGF-II. Effects on cell proliferation and apoptosis as well as on the expression of the proto-oncogene c-myc were studied.Results-In this study we show that Tera 2 cells deprived of serum undergo programmed cell death (apoptosis). The onset of nuclear fragmentation was observed 12 hours after serum withdrawal. The morphological changes of the Tera 2 cell nuclei were confirmed by the occurrence of a nucleosome ladder. However, the constitutive expression of the proto-oncogene c-myc was not decreased in parallel with initiation of apoptosis. The apoptotic response to serum withdrawal could be counteracted by simultaneous addition of IGF-II. In addition it was found that human testicular tumours (seminoma and embryonal carcinoma) contain raised levels of insulin-like growth factors.Conclusions-The precise roles of IGF-I and IGF-II have been unclear, and there is overwhelming evidence against these factors as primarily transforming agents. The finding that IGF-II apparently counteracts apoptosis in vitro may well explain its effects on tumours in vivo.
目的——研究胰岛素样生长因子II(IGF-II)如何影响人畸胎瘤细胞的行为。方法——在有无IGF-II的情况下,将人多能性畸胎瘤细胞系Tera 2在无血清条件下培养。研究其对细胞增殖、凋亡以及原癌基因c-myc表达的影响。结果——在本研究中,我们发现血清剥夺的Tera 2细胞会经历程序性细胞死亡(凋亡)。血清撤除后12小时观察到核碎裂的开始。核小体梯带的出现证实了Tera 2细胞核的形态变化。然而,原癌基因c-myc的组成性表达并未随着凋亡的启动而平行下降。同时添加IGF-II可抵消血清撤除引起的凋亡反应。此外,发现人类睾丸肿瘤(精原细胞瘤和胚胎癌)中胰岛素样生长因子水平升高。结论——IGF-I和IGF-II的确切作用尚不清楚,并且有大量证据反对将这些因子作为主要的转化因子。IGF-II在体外明显抵消凋亡这一发现很可能解释了其在体内对肿瘤的影响。