Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner. 2006

Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
Department of Biochemistry and Molecular Genetics, University of Illinois, Chicago, Illinois 60607, USA.

Akt contributes to tumorigenesis by inhibiting apoptosis. Here we establish that Akt is required for normal cell proliferation and susceptibility to oncogenesis independently of its antiapoptotic activity. Partial ablation of Akt activity by deleting Akt1 inhibits cell proliferation and oncogenesis. These effects are compounded by deleting both Akt1 and Akt2. In vivo, Akt1 null mice are resistant to MMTV-v-H-Ras-induced tumors and to skin carcinogenesis. Thus, partial ablation of Akt activity is sufficient to suppress tumorigenesis in vitro and in vivo. The effect of Akt deficiency on cell proliferation and oncogenesis is p53 independent but mTORC1 dependent. Surprisingly, upon mTORC1 hyperactivation, the reduction in Akt activity does not impair cell proliferation and susceptibility to oncogenic transformation; thus, Akt may mediate these processes exclusively via mTORC1.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002472 Cell Transformation, Viral An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus. Transformation, Viral Cell,Viral Cell Transformation,Cell Transformations, Viral,Transformations, Viral Cell,Viral Cell Transformations
D003433 Crosses, Genetic Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species. Cross, Genetic,Genetic Cross,Genetic Crosses
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic

Related Publications

Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
February 2018, Scientific reports,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
February 2016, Cell death & disease,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
April 2015, Nature communications,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
August 2021, Cell cycle (Georgetown, Tex.),
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
November 2019, Scientific reports,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
June 2020, European journal of nutrition,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
January 2020, Toxicology and applied pharmacology,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
May 2010, Cell metabolism,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
July 2015, Blood,
Jennifer E Skeen, and Prashanth T Bhaskar, and Chia-Chen Chen, and William S Chen, and Xiao-ding Peng, and Veronique Nogueira, and Annett Hahn-Windgassen, and Hiroaki Kiyokawa, and Nissim Hay
February 2023, Journal of natural products,
Copied contents to your clipboard!