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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Hui Fata, Jimmie E. Bissell, Mina J. Roth, Richard A. Nelson, Celeste M. Liu, Hong Radisky, Derek C. |
| Description | Author Affiliation: Liu H ( Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.); |
| Abstract | Akt1 is frequently up-regulated in human tumors and has been shown to accelerate cell proliferation and to suppress programmed cell death; consequently, inhibition of the activity of Akt1 has been seen as an attractive target for therapeutic intervention. Paradoxically, hyperactivation of the Akt1 oncogene can also prevent the invasive behavior that underlies progression to metastasis. Here we show that overexpression of activated myr-Akt1 in human breast cancer cells phosphorylates and thereby targets the tumor suppressor tuberous sclerosis complex 2 (TSC2) for degradation, leading to reduced Rho-GTPase activity, decreased actin stress fibers and focal adhesions, and reduced motility and invasion. Overexpression of TSC2 rescues the migration phenotype of myr-Akt1-expressing tumor cells, and high levels of TSC2 in breast cancer patients correlate with increased metastasis and reduced survival. These data indicate that the functional properties of genes designated as oncogenes or tumor suppressor genes depend on the context of the cell type and the tissues studied, and suggest the need for caution in designing therapies targeting the function of individual genes in epithelial tissues. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 11 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Breast Neoplasms Genetics Proto-Oncogene Proteins C-akt Physiology Tumor Suppressor Proteins Animals Pathology Physiopathology Cell Line, Tumor Cell Movement Focal Adhesions Mice Mice, Nude Neoplasm Invasiveness Neoplasm Transplantation Oncogenes Transplantation, Heterologous Rho GTP-Binding Proteins Antagonists & Inhibitors Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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