Akt isoform-specific inhibition of MDA-MB-231 cell proliferation

作者：Yang Wonseok; Ju Ji hyun; Lee Kyung min; Shin Incheol^*

来源：Cellular Signalling, 2011, 23(1): 19-26.

DOI：10.1016/j.cellsig.2010.07.016

• Akt isoforms
• Breast cancer
• CDK2
• ERK
• p27

To dissect the isoform-specific roles of Akt in breast cancer cells, constitutively active Akt isoforms were introduced into MDA-MB-231 cells. Both Akt1 and Akt2 efficiently inhibited the growth of MDA-MB-231 cells. Overexpression of Akt1 down-regulated ERK activity inhibiting Ser 259 phosphorylation of c-Raf and subsequent downstream signaling. Akt2 overexpression up-regulated the cell cycle inhibitor p27. Cycloheximide decay assays showed that Akt2 increased the stability and nuclear localization of p27, thus inhibiting the cyclin E/CDK2 complex. These results suggest that the inhibition of cell proliferation by Akt1 and Akt2 is mediated by isoform-specific mechanisms.

• 出版日期2011-1