Sequential protooncogene expression during rat liver regeneration.

Sequential protooncogene expression during rat liver regeneration.
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DOI:
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发表时间:
1986-06
期刊:
影响因子:
11.2
通讯作者:
N. Thompson;J. Mead;L. Braun;M. Goyette;P. Shank;N. Fausto
N. Thompson;J. Mead;L. Braun;M. Goyette;P. Shank;N. Fausto
中科院分区:
医学1区
文献类型:
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作者:
N. Thompson;J. Mead;L. Braun;M. Goyette;P. Shank;N. Fausto

文献摘要

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当通过部分肝切除刺激正常静止的成年大鼠肝脏中的生长时,c-fos、c-myc 和 p53 的信使 RNA (mRNA) 的稳态水平在 DNA 合成之前的复制前阶段依次增加。部分肝切除术后 15 分钟内,c-fos mRNA 水平至少升高 4 倍,并在 2 小时内迅速下降;术后 30 分钟至 2 小时内,c-myc mRNA 达到最高水平(正常的 5 倍)。 c-fos 和 c-myc 表达的第二个瞬时阶段发生在部分肝切除术后 8 小时左右。 p53 mRNA 水平在术后 8 至 12 小时内增加(比正常值高 5 倍),并反映在部分肝切除术后 12 至 15 小时内 p53 蛋白稳态水平的升高。 ras p21 蛋白的水平在 DNA 复制和细胞分裂活跃的后期才增加。部分肝切除术时注射的放线菌素 D 可阻断 2 小时内 c-myc 的增加,但对 c-fos mRNA 水平没有影响。 6小时注射的放线菌素D仅部分阻断8小时时c-myc和p53 mRNA的增加,但不影响c-fos mRNA。我们的结果表明,在肝再生的复制前阶段,原癌基因的瞬时和连续表达可能反映了与肝细胞进入和进展到细胞周期相关的事件,并且可以作为识别参与肝再生的特定体液因子的标记。
When growth is stimulated in the normally quiescent adult rat liver by partial hepatectomy, steady state levels of messenger RNAs (mRNAs) for c-fos, c-myc, and p53 increase sequentially during the prereplicative phase which precedes DNA synthesis. Levels of c-fos mRNA are elevated at least 4-fold within 15 min after partial hepatectomy and decrease rapidly by 2 h; c-myc mRNA reaches maximal levels (5-fold over normal) between 30 min and 2 h after the operation. A second, transient phase of expression for both c-fos and c-myc occurs around 8 h after partial hepatectomy. p53 mRNA levels increase between 8 and 12 h after the operation (5-fold over normal) and are reflected in an elevation of steady state levels of p53 protein between 12 and 15 h after partial hepatectomy. The levels of ras p21 protein increase much later at a time of active DNA replication and cell division. Actinomycin D injected at the time of partial hepatectomy blocks the increase in c-myc at 2 h but has no effect on c-fos mRNA levels. Actinomycin D injected at 6 h only partially blocks the increase in c-myc and p53 mRNA at 8 h but does not affect c-fos mRNA. Our results suggest that the transient and sequential expression of protooncogenes during the prereplicative stage of liver regeneration is likely to reflect events associated with entry and progression of hepatocytes into the cell cycle and can serve as markers for identifying specific humoral factors involved in liver regeneration.