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Activation of Akt2 Inhibits anoikis and apoptosis induced by myogenic differentiation
Y Fujio1, Y Mitsuuchi, J R Testa
1Division of Cardiovascular Research, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
Abstract:
Akt2, a homolog of Akt1, encodes a serine/threonine protein kinase that is amplified in ovarian and pancreatic cancers. The antiapoptotic activities of the Akt1 proto-oncogene product have been well documented, but the role of Akt2 in cellular survival is poorly understood. Here, we demonstrate that Akt2 mRNA, protein and kinase activity are upregulated during serum deprivation-induced C2C12 cell myogenic differentiation, a process that is associated with the acquisition of an apoptosis-resistant phenotype. Transient transfection of plasmids encoding wild-type and constitutively-active Akt2 conferred resistance against apoptosis in differentiating C2C12 cells, while a kinase-negative Akt2 construct did not. Adenovirus-mediated transfer of the constitutively-active Akt2 cDNA also suppressed apoptosis during serum deprivation-induced myogenic differentiation and it protected cells from apoptosis induced by cell detachment. These data indicate that Akt2 functions as an anti-apoptotic gene during cellular differentiation, a property that may contribute to its oncogenicity.
Insights
Akt2 (a protein kinase) promotes cell survival during differentiation. Upregulated Akt2 confers resistance to apoptosis, suggesting a role in cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Akt1's anti-apoptotic role is known, but Akt2's function in cell survival is unclear.
- Akt2 is amplified in ovarian and pancreatic cancers, hinting at its oncogenic potential.
Purpose of the Study:
- To investigate the role of Akt2 in cellular survival during differentiation.
- To determine if Akt2 confers resistance to apoptosis.
Main Methods:
- Studied Akt2 expression (mRNA, protein, kinase activity) during C2C12 cell differentiation.
- Used transient transfection and adenovirus-mediated gene transfer to manipulate Akt2 activity.
- Assessed apoptosis resistance under various conditions, including serum deprivation and cell detachment.
Main Results:
- Akt2 expression and activity increased during serum deprivation-induced myogenic differentiation.
- Overexpression of wild-type and constitutively-active Akt2 protected differentiating cells from apoptosis.
- Kinase-inactive Akt2 did not confer apoptosis resistance.
- Akt2 protected cells from apoptosis induced by cell detachment.
Conclusions:
- Akt2 acts as an anti-apoptotic gene during cellular differentiation.
- Its anti-apoptotic function may contribute to its oncogenic properties in cancer.