Table of Contents
Definition / general | Terminology | Pathophysiology | Clinical features | Uses by pathologists | Microscopic (histologic) images | Virtual slides | Positive staining - normal | Positive staining - disease | Negative staining | Additional referencesCite this page: Satbir T. Akt. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsAKT.html. Accessed December 10th, 2019.
Definition / general
- The Akt family is comprised of 3 closely related serine / threonine protein kinases (Akt1, Akt2 and Akt3), which regulate many processes including metabolism, proliferation, cell survival, growth, inhibition of apoptosis and angiogenesis
- These kinases phosphorylate serine or threonine residues on a range of downstream substrates
- They are activated by various factors such as insulin, PI3K, IGF1
- Akt was named after a cell transforming retrovirus isolated from a spontaneous thymoma in AKR mice (Proc Natl Acad Sci U S A 1987;84:5034)
- Due to its involvement in various cellular processes that promote cell survival and growth, the AKT pathway is a major target for cancer drug discovery
Terminology
- "Akt" usually refers to Akt1
- AKT1 is also called RAC-alpha serine / threonine protein kinase, v-akt murine thymoma viral oncogene homolog 1, and protein kinase B (PKB), and is encoded by the AKT1 gene
Pathophysiology
Clinical features
- Akt is associated with tumor cell survival, proliferation and invasiveness
- The activation of Akt is one of the most frequent alterations observed in human cancer and tumor cells
- Tumor cells that have constantly active Akt may depend on Akt for survival, so understanding Akt and its pathways is important
- A mosaic activating mutation (c. 49G→A, p.Glu17Lys) in AKT1 is associated with Proteus Syndrome, which causes overgrowth of skin, connective tissue, brain and other tissues (Wikipedia - Protein kinase B)
- AKT-GSK3B signaling is a target of lithium and has been implicated in the pathogenesis of mood disorders, and has a role in schizophrenia (Nat Genet 2004;36:131)
- A somatic mutation at amino acid 17 of AKT1, resulting in glutamic acid to lysine substitution, has been observed in human breast, colorectal and ovarian cancers
- This mutation activates AKT1 and localizes it to the plasma membrane, stimulating downstream signaling, resulting in cell transformation and induction of leukemia in mice (Nature 2007;448:439)
- Mutations resulting in upregulation of AKT1 phosphorylated at Thr308 have been shown to be involved in Cowden syndrome (Am J Hum Genet 2013;92:76)
- Dysregulation of the AKT1 pathway may be important in the pathogenesis of intrahepatic cholangiocarcinoma (Mod Pathol 2012;25:131)
- Akt pathway may induce autophagy in cancer cells (J Biol Chem 2012;287:25325)
Mice models:
- These mice displayed impaired skin development due to a proliferation defect, skeletal muscle atrophy due to a marked decrease in individual muscle cell size, and impaired bone development (Genes Dev 2003;17:1352)
Uses by pathologists
- Pathways involving AKT signaling are upregulated in a variety of cancers
- Phosphorylation of Akt1 is associated with a poor prognosis in early breast cancer
- Tumors with high levels of Akt1 have been associated with tamoxifen and doxorubicin resistance, resulting in poor prognostic outcome (J Pathol 2012;227:481)
Microscopic (histologic) images
Positive staining - normal
- Uterus, cervix, ovary, testis, lung, liver (adult), lymph node, brain (fetal), peripheral blood mononuclear cells
Positive staining - disease
- Most malignancies show moderate to strong nuclear AKT staining
Negative staining
- Brain (adult), hair follicle, liver (fetal), bone, colon muscle, nasopharynx, T cells
Additional references
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