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Title   Wild - type p53 유전자가 결여된 암세포에서 Cyclic AMP 의 세포주기 조절기작에 관한 연구 ( Cell Cylce Regulatory Effects of Cyclic AMP in Cancer Cells Which Lack Wild - type p53 )
Publicationinfo   2000 Jan; 032(04): 750-757.
Key_word   Dibutyryl-cAMP, Cell cycle regulation
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Abstract   Purpose: The activator of protein kinase A, cyclic AMP, has been a recognized growth inhibitor of certain cell types. The present study aimed to investigate the effects of dibutyryl cAMP on the growth of cancer cells which lack wild-type p53 and to determine the mechanism of growth inhibition. Materials and Methods: Prostate and breast cancer cells were treated with dibutyryl cAMP and compared with untreated cells. Growth patterns of cells were assessed by trypan blue-excluding method and western blot was done to determine protein levels of cell cycle regulatory proteins which govern Gl and Gl/S phase. Northern blot and immunoprecipitation were done to determine the level of mRNA of p21 and the association between cell cycle regulatory proteins. In vitro immune complex kinase assay was done to assess the activity of cdk2. Results: cAMP reduced cell growth by 48 h. Cyclin D3 level was downregulated and RB protein level was decreased and mostly unphosphorylated forms remained. The association of RB with E2F1 was increased. While cdk2 levels remained constant throughout cAMP treatment, the activity of cdk2/cyclin E complex, which is responsible for entry into S phase, was downregulated. Cdk inhibitors, p27 and p21 were induced with cAMP treatment. Conclusion: These observation suggest that the growth inhibitory effects of dibutyryl cAMP on prostate and breast cancer cells were mediated by induction of cdk inhibitors such as p21 and p27 and RB activation in accordance with downregulation of cdk2.
저 자   장정순(Joung Soon Jang),강정훈(Joung Hun Kang),박병규(Byung Kiu Park),황상구(Sang Gu Hwang)