Differential Effects of Akt Isoforms on Motility and Proliferation of MDA231 Breast Cancer Cells

초록

The Akt family of kinases are well known to be activated by growth factors and to regulate pleiotropic cellular activities. However, there are limited information about the specificities of three Akt isoforms. To gain insight into isoform-specific roles for Akt, transfection studies were performed in MDA-MB-231 breast cancer cells using constitutively active (myristoylated) Akt isoforms. We have investigated cell motility, a key phenotype of invasive carcinomas and cell proliferation. Wound healing assays revealed that Akt1 overexpressing MDA-MB-231 cells showed decrease in mobility while Akt2 and Akt3 overexpression did not significantly affect motility of the transfected cells. Proliferation assays indicated that forced expression of Akt1 inhibited growth of MDA-MB-231 cells while Akt2 and Akt3 led to an increase in cell proliferation. Down-regulation of MAPK and c-Jun phosphorylation in MDA-MB-231-Akt1 cells suggested that cross-talk between Akt and MAPK signaling might be responsible for this interesting phenomena.