Adenovirus-mediated gene transfer of MMAC1/PTEN to glioblastoma cells inhibits S phase entry by the recruitment of p27Kip1 into cyclin E/CDK2 complexes.
作者： M. Ramachandra , I. W. Cheney , M.-T. Vaillancourt , S. T. C. Neuteboom , R. Bookstein
DOI:
关键词:
摘要: Genetic alterations in the MMAC1 tumor suppressor gene (also referred to as PTEN or TEP1) occur several types of human cancers including glioblastoma. Growth suppression induced by overexpression cells with mutant alleles is thought be mediated inhibition signaling through phosphatidylinositol 3-kinase pathway. However, exact biochemical mechanisms which exerts its growth-inhibitory effects are still unknown. Here we report that recombinant adenovirus-mediated three different MMAC1-mutant glioblastoma cell lines blocked progression from G0/G1 S phase cycle. Cell cycle arrest correlated recruitment cyclin-dependent kinase (CDK) inhibitor, p27Kip1, cyclin E immunocomplexes, resulted a reduction CDK2 activities and decrease levels endogenous phosphorylated retinoblastoma protein. CDK4 were unaffected, CDK inhibitor p21Cip1 present immunocomplexes. Therefore, via transfer suppresses growth inhibitory mechanisms, such, represents potential therapeutic approach treating glioblastomas.
aacrjournals.org参考文章(39)
R. A. Kerr, Ice Rhythms—Core Reveals a Plethora of Climate Cycles Science. ,vol. 274, pp. 499- 500 ,(1996) , 10.1126/SCIENCE.274.5287.499
H-J. Su Huang, Webster K. Cavenee, Frank B. Furnari, The Phosphoinositol Phosphatase Activity of PTEN Mediates a Serum-sensitive G1 Growth Arrest in Glioma Cells Cancer Research. ,vol. 58, pp. 5002- 5008 ,(1998)
Takahisa Takino, Masahito Tamura, Jianguo Gu, Kenneth M. Yamada, Tumor Suppressor PTEN Inhibition of Cell Invasion, Migration, and Growth: Differential Involvement of Focal Adhesion Kinase and p130Cas Cancer Research. ,vol. 59, pp. 442- 449 ,(1999)
Christa Miliaresis, Christa Miliaresis, Nicholas Tonks, Nicholas Tonks, Ramon Parsons, Ramon Parsons, Laura Simpson, Laura Simpson, Michael P. Myers, Michael P. Myers, Jing Li, Jing Li, Michelle Takahashi, Michelle Takahashi, The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene. Cancer Research. ,vol. 58, pp. 5667- 5672 ,(1998)
Cangi Mg, Chiaur Ds, Loda M, Pagano M, Signoretti S, Lipman J, Singh Sp, Aizenman L, Goldman H, Ellis Fh, Loss or Altered Subcellular Localization of p27 in Barrett's Associated Adenocarcinoma Cancer Research. ,vol. 58, pp. 1730- 1735 ,(1998)
J Avanzini, S V Tavtigian, K N Wills, I W Cheney, P W Shabram, G W Demers, A Morimoto, R Bookstein, M T Vaillancourt, J B Bolen, D E Johnson, Suppression of tumorigenicity of glioblastoma cells by adenovirus-mediated MMAC1/PTEN gene transfer. Cancer Research. ,vol. 58, pp. 2331- 2334 ,(1998)
H Matsushime, D E Quelle, S A Shurtleff, M Shibuya, C J Sherr, J Y Kato, D-type cyclin-dependent kinase activity in mammalian cells. Molecular and Cellular Biology. ,vol. 14, pp. 2066- 2076 ,(1994) , 10.1128/MCB.14.3.2066
Erguang Li, Dwayne Stupack, Richard Klemke, David A. Cheresh, Glen R. Nemerow, Adenovirus endocytosis via alpha(v) integrins requires phosphoinositide-3-OH kinase. Journal of Virology. ,vol. 72, pp. 2055- 2061 ,(1998) , 10.1128/JVI.72.3.2055-2061.1998
M. P. Myers, J. P. Stolarov, C. Eng, J. Li, S. I. Wang, M. H. Wigler, R. Parsons, N. K. Tonks, P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 9052- 9057 ,(1997) , 10.1073/PNAS.94.17.9052
V Dulic, E Lees, S. Reed, Association of human cyclin E with a periodic G1-S phase protein kinase. Science. ,vol. 257, pp. 1958- 1961 ,(1992) , 10.1126/SCIENCE.1329201