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大多數的癌症化學治療均以破壞細胞去氧核醣核酸(DNA)為毒殺癌細胞的
機轉,而細胞在DNA遭到破壞後,會停滯在細胞週期的G2期,而不能進行有絲
分裂(mitosis),DNA破壞如何能造成細胞週期停滯,其機轉目前並不清楚。
根據最近的研究發現,在正常情形下細胞要進行有絲分裂需要一種有絲分
裂促進因子(MPF)的作用,MPF的主成份是一種蛋白質p34cdc2,這是一種蛋
白質激■(kinase),可以磷酸化許多其他蛋白質而促成有絲分裂。另一種
蛋白質則為乙型細胞週期素(cyclin B),它的特性是濃度隨著細胞週期而
增加;即在S期開始聚積,G2/M期達到最高點,最後cyclin B蛋白質在有絲分
裂末期迅速遭到分解。在有絲分裂之前,cyclin B的聚積是活化p34cdc2所
必須的,而最近的研究發現細胞在DNA破壞之後,cyclin B蛋白質不能聚積,
這可能是 p34cdc2不能活化,細胞不能分裂,停滯在G2的原因之一。而在本
研究中我們進一步發現當細胞DNA受到破壞後,cyclin B mRNA的聚積亦下
降,由於 cyclin B mRNA聚積下降可能是cyclin B mRMA不能被製造或者是
因為RNA的穩定度下降所造成,為了進一步了解cyclin B基因表現受到抑制
的原因,我們以核內延長法(muclear run on)來分析。結果發現cyclin B
mRNA製造率並沒有下降,故可能是由於RNA穩定度降低,使cyclin B基因的
表現受到抑制。
After treated with anticancer drug, most tumor cells are
arrested at G2 phase of cell cycle before cell death occurred.
Mechanism of failure of mitosis is not clear. According to
recent findings, the activation of mitosis promoting factor
(MPF) is essential for cells to progress into mitosis. MPF is a
protein complex composed of cyclin B protein and p34cdc2
protein. p34cdc2 is a potent protein kinase that will
phosphorylate a series of nuclear proteins and induce mitosis.
Cyclin B is gradually accumulated throughout the S phase and G2/
M phase of cell cycle and rapidly degraded after mitosis.
Cyclin B will form complexed with p34cdc2 and activate p34cdc2,
the protein kinase. The recent finding rvealed the cyclin B
protein fail to accumulate after DNA damage This might be the
reason why p34cdc2 fail to be activated and mitosis fail to
accur after DNA damage. We studied the gene expression of
cyclin B after DNA damage. The results showed that cyclin B
mRNA also fail to accumulate. Because decreased cyclin B
synthesis can be due to the degradation of cyclin B mRNA or
inhibition of cyclin B mRNA synthesis, we monitor cyclin B
synthesis by nuclear run on experiment. Results showed that
cyclin B mRNA synthesis is not inhibited. It is possible that
the stability of cyclin B mRNA is reduced.
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