Altered regulation of c-myc expression in adenovirus-transformed cells.

A W Braithwaite, K E Fry, S LeJeune, H Naora
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Abstract

Expression of the oncogenes c-myc, c-raski, and p53 is studied in normal primary mouse cultures and in two adenovirus-transformed mouse cell lines. In all cases oncogene expression is measured in cells arrested in G1 (or G0 for primary cells) by serum starvation and at different times after cell cycle traverse is stimulated by addition of high serum. For primary mouse cells, c-myc mRNA levels are found to increase four- to six-fold within 1 h of serum addition and then decline by 4 h to nearly the level observed in serum-starved cells. This level is maintained throughout the remainder of the cell cycle. The early induction of c-myc is dependent on serum concentration and is independent of cell density. These results confirm and extend previous observations for primary cells. By contrast, expression of c-raski does not vary at all through the cell cycle and p53 increases with time after mitogenic stimulation. In the adenovirus-transformed cell lines, the regulation of expression of c-myc with respect to the cell cycle is altered. There is an increase in c-myc in S phase cells which is dependent on cell density and the early induction in response to serum addition as seen in primary cells is absent. Expressions of c-raski and p53 are found to show similar profiles to those observed for primary cells.

腺病毒转化细胞中c-myc表达调控的改变
在正常原代小鼠培养物和两种腺病毒转化小鼠细胞系中研究了癌基因c-myc、c-raski和p53的表达。在所有情况下,通过血清饥饿在G1期(或原代细胞为G0期)捕获的细胞中以及在细胞周期穿越后通过添加高血清刺激的不同时间测量癌基因表达。对于原代小鼠细胞,c-myc mRNA水平在添加血清1小时内增加4至6倍,然后在4小时内下降到接近血清饥饿细胞的水平。这一水平在细胞周期的剩余时间内保持不变。c-myc的早期诱导依赖于血清浓度,与细胞密度无关。这些结果证实并扩展了先前对原代细胞的观察。相比之下,c-raski的表达在整个细胞周期中完全没有变化,而p53在有丝分裂刺激后随着时间的推移而增加。在腺病毒转化的细胞系中,c-myc的表达调控与细胞周期有关。在S期细胞中,c-myc的增加取决于细胞密度,而在原代细胞中,对血清添加反应的早期诱导则不存在。c-raski和p53的表达与原代细胞相似。
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