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At least 19 recordsLinked to original sources
PubMed1991

A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region.

The v-akt oncogene codes for a 105-kilodalton fusion phosphoprotein containing Gag sequences at its amino terminus. Sequence analysis of v-akt and biochemical characterization of its product revealed that it codes for a protein kinase C-related serine-threonine kinase whose cellular homolog is expressed in most tissues, with the highest amount found in thymus. Although Akt is a serine-threonine kinase, part of its regulatory region is similar to the Src homology-2 domain, a structural motif characteristic of cytoplasmic tyrosine kinases that functions in protein-protein interactions. This suggests that Akt may form a functional link between tyrosine and serine-threonine phosphorylation pathways.

Amino Acid Sequence↗
PubMed1987

Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma.

A previous report described the isolation of a directly transforming retrovirus, AKT8, from a spontaneous thymoma of an AKR mouse. The AKT8 provirus has now been molecularly cloned from a transformed, nonproducer cell line. The virus genome contains both viral and nonviral, cell-related sequences; the nonviral sequence has been designated v-akt, the presumed viral oncogene of the AKT8 virus. This gene lacks homology to the 16 other oncogenes tested. The cloned provirus has undergone a partial deletion, during cell passage in vitro, that prevents direct demonstration of the transforming ability of this molecular clone. Two human homologues of the v-akt oncogene, AKT1 and AKT2, were cloned. A survey of 225 human tumors for changes involving AKT1 led to the discovery of a 20-fold amplification of this gene in one of the five gastric adenocarcinomas tested. The results demonstrate that AKT8 has the characteristic structure of a directly transforming retrovirus and that it contains a gene derived from highly conserved cellular sequences that may be involved in the pathogenesis of some human malignancies.

Adenocarcinoma↗
PubMed1993

The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential.

The acute retrovirus AKT8, isolated from an AKR mouse T-cell lymphoma, transforms mink lung cells in culture and is oncogenic when inoculated into newborn mice. The oncogene carried by this virus, v-akt, arose by recombination between Gag and the 5' untranslated region of the cellular gene c-akt. v-akt encodes a 105 kilodalton (kd) Gag-Akt fusion protein which is phosphorylated on serine and threonine residues. c-akt encodes a 55 kd serine-threonine protein-kinase, which is related to members of the protein kinase C (PKC) family and contains an SH2-like domain. The SH2-like and catalytic domains of Akt were expressed in E. coli as fusions to the carboxy-terminus of the Maltose binding protein (MBP). Antibodies against these proteins were raised in rabbits and they were used to determine the potential myristylation and subcellular localization of the v-akt and c-akt protein products. Immunoprecipitation of v-akt and c-akt from lysates of [35S]methionine and [3H]myristic acid labeled AKT8 transformed mink lung cells revealed that only v-akt was myristylated. Fractionation of Dounce-homogenized cellular extracts from uninfected and v-akt-transformed mink lung and PA317 cells and from uninfected PC12 cells by differential centrifugation showed that while the c-akt protein was localized primarily in the cytosol (90%), the v-akt protein was dispersed among the cellular compartments with approximately 40% on the plasma membranes, approximately 30% in the nucleus and approximately 30% in the cytosol. To determine whether the differences in post-translational modification and subcellular distribution between c-akt and v-akt translated into oncogenicity differences between the two proteins, we used retrovirus based constructs to express them both in the nontumorigenic rat T cell lymphoma line 5675. Intraperitoneal (IP) inoculation of the parental and c-akt expressing 5675 cells in nude Balb/c mice revealed that neither was oncogenic. In sharp contrast to these results, v-akt expressing 5675 cells inoculated in nude Balb/c mice were found to be highly oncogenic.

Amino Acid Sequence↗
PubMed1998

Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis.

Oncogenesis is a complicated process involving signal transduction pathways that mediate many different physiological events. Typically, oncogenes cause unregulated cell growth and this phenotype has been attributed to the growth-stimulating activity of oncogenes such as ras and src. In recent years, much research effort has focused on proteins that function downstream of Ras, leading to the identification of the Ras/Raf/MAPK pathway, because activation of this pathway leads to cellular proliferation. Activated receptor tyrosine kinases (RTKs) also utilize this pathway to mediate their growth-stimulating effects. However, RTKs activate many other signaling proteins that are not involved in the cellular proliferation process, per se and we are learning that these pathways also contribute to the oncogenic process. In fact, RTKs and many of the proteins involved in RTK-dependent signal transduction can also function as oncogenes. For example, the catalytic subunit of phosphoinositide 3-kinase (P13-K) was recently identified as an oncogenic protein. The scope of pathways that are activated by oncogenic RTKs is expanding. Thus, not only do RTKs activate Ras-dependent pathways that drive proliferation, RTKs activate P13-K-dependent pathways which also contribute to the oncogenic mechanism. P13-K can initiate changes in gene transcription, cytoskeletal changes through beta-catenin, changes in cell motility through the tumor suppressor, adenomatous polyposis coli (APC), and phosphorylation of BAD, a protein involved in apoptotic and antiapoptotic signaling. There is also cross-talk between RTKs and the oncostatin cytokine receptor which may positively and negatively influence oncogenesis. For this review, we will focus on oncogenic RTKs and the network of cellular proteins that are activated by RTKs because multiple, divergent pathways are responsible for oncogenesis.

Animals↗
PubMed1997

Growth factor stimulation of hematopoietic cells leads to membrane translocation of AKT1 protein kinase.

AKT1 is the human homolog of the v-akt oncogene. AKT1 has two distinct protein domains, one serine/threonine kinase domain and one pleckstrin homology (PH) domain. We studied the expression and activity of AKT1 in hematopoietic cell lines. The expression of AKT1 was constitutive in hematopoietic cells of various stages of development. In the growth factor dependent MO7e cells, serum and growth factor starvation resulted in an early 50% fall in activity which was maintained over 24 h. Treatment of cells which growth factors or agents which induce differentiation activated AKT1. The subcellular localization of AKT1 in MO7e cells was altered as it was activated. High AKT1 kinase activity was associated with membrane fractions in stimulated cells, in contrast to the much lower AKT1 activity in membranes of cells starved of serum and growth factor for 1 h. These results demonstrate AKT1 kinase activity and its regulation by extracellular signaling factors in vivo in hematopoietic cells, and suggest that the activation of AKT1 involves intracellular translocation of the kinase from cytosol to membrane.

Biological Transport↗
PubMed1992

Conservation analysis and structure prediction of the SH2 family of phosphotyrosine binding domains.

Src homology 2 (SH2) regions are short (approximately 100 amino acids), non-catalytic domains conserved among a wide variety of proteins involved in cytoplasmic signaling induced by growth factors. It is thought that SH2 domains play an important role in the intracellular response to growth factor stimulation by binding to phosphotyrosine containing proteins. In this paper we apply the techniques of multiple sequence alignment, secondary structure prediction and conservation analysis to 67 SH2 domain amino acid sequences. This combined approach predicts seven core secondary structure regions with the pattern beta-alpha-beta-beta-beta-beta-alpha, identifies those residues most likely to be buried in the hydrophobic core of the native SH2 domain, and highlights patterns of conservation indicative of secondary structural elements. Residues likely to be involved in phosphotyrosine binding are shown and orientations of the predicted secondary structures suggested which could enable such residues to cooperate in phosphate binding. We propose a consensus pattern that encapsulates the principal conserved features of the SH2 domains. Comparison of the proposed SH2 domain of akt to this pattern shows only 12/40 matches, suggesting that this domain may not exhibit SH2-like properties.

Amino Acid Sequence↗
PubMed1998

Suppression of transforming growth factor-beta-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway.

Insulin and insulin receptor substrate 1 (IRS-1) are capable of protecting liver cells from apoptosis induced by transforming growth factor-beta1 (TGF-beta). The Ras/mitogen-activated protein kinase (MAP kinase) and the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathways are both activated upon insulin stimulation and can protect against apoptosis under certain circumstances. We investigated which of these pathways is responsible for the protective effect of insulin on TGF-beta-induced apoptosis. An activated Ras, although elicited a strong mitogenic effect, could not protect Hep3B cells from TGF-beta-induced apoptosis. Furthermore, PD98059, a selective inhibitor of MEK, did not suppress the antiapoptotic effect of insulin. In contrast, the PI 3-kinase inhibitor, LY294002, efficiently blocked the effect of insulin. Protection against TGF-beta-induced apoptosis conferred by PI 3-kinase was further verified by stable transfection of an activated PI 3-kinase. Downstream targets of PI 3-kinase involved in this protection was further investigated. An activated Akt mimicked the antiapoptotic effect of insulin, whereas a dominant-negative Akt inhibited such effect. However, rapamycin, the p70S6 kinase inhibitor, had no effect on the protectivity of insulin against TGF-beta-induced apoptosis, suggesting that the antiapoptotic target of PI 3-kinase/Akt pathway is independent or lies upstream of the p70S6 kinase. The mechanism by which PI 3-kinase/Akt pathway interferes with the apoptotic signaling of TGF-beta was explored. Activation of PI 3-kinase did not lead to a suppression of Smad hetero-oligomerization or nuclear translocation but blocked TGF-beta-induced caspase-3-like activity. In summary, the PI 3-kinase/Akt pathway, but not the Ras/MAP kinase pathway, protects against TGF-beta-induced apoptosis by inhibiting a step downstream of Smad but upstream of caspase-3.

Apoptosis↗
PubMed1999

Anti-apoptotic function of Rac in hematopoietic cells.

The small GTP-binding protein Rac plays a pivotal role in the regulation of diverse physiological events including reorganization of the actin cytoskeleton, cell cycle progression, and transformation. Here we show an anti-apoptotic effect of Rac in interleukin-3-dependent murine hematopoietic BaF3 cells. Activated Rac(G12V), when ectopically expressed in BaF3 cells, rendered the cells resistant to apoptosis upon interleukin-3 deprivation, while activated mutants of Rho and Cdc42 displayed no significant anti-apoptotic effect. In contrast to activated Ras, which also supports cell survival in the absence of interleukin-3, Rac required fetal bovine serum for the prevention of cell death. The involvement of phosphatidylinositol 3-kinase downstream of Rac was demonstrated by the inhibition of Rac-induced cell survival by wortmannin and LY294002 and the presence of phosphatidylinositol kinase activity in the Rac immunoprecipitate. Furthermore, the serine/threonine kinase Akt was stimulated by activated Rac and fetal bovine serum in a synergistic manner. Rac-induced Akt activation was mediated by phosphorylation of threonine-308 and serine-473. In addition to the phosphatidylinositol 3-kinase/Akt pathway, the p38 mitogen-activated protein kinase pathway was crucial for Rac-dependent survival, whereas p38 mitogen-activated protein kinase nas not implicated in Ras-induced anti-apoptotic signaling. These findings provide evidence for the involvement of Rac in survival signaling of hematopoietic cells.

Animals↗
PubMed1993

Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications.

Sequence analysis of a nearly full-length murine c-akt cDNA clone and comparison with v-akt revealed the following: (a) The entire coding region of c-akt is identical to that of v-akt with the exception of five G to A transitions that do not alter the reading frame. The 3' untranslated regions of v-akt and c-akt are also identical with the exception of three single-base differences. (b) The recombination event that gave rise to v-akt occurred between the virus at nucleotide 785 from the Gag ATG codon and the 5' untranslated region of c-akt to 60 bp 5' from the c-akt ATG codon. (c) Three nucleotides absent from both Gag and c-akt were inserted at the junction between the two genes. The outcome of these events was to place, in frame, a 63-bp fragment between Gag and Akt. The resulting v-akt oncogene is predicted to encode a tripartite Gag (p12, p15, delta p30)-X-c-akt protein product. The c-akt protein contains, starting from its amino terminus, a src homology 2-like (SH2-like) domain, a domain rich in glutamic acid residues, part of which is predicted to form an amphipathic helix, and a kinase domain encoding a serine-threonine kinase with high degree of homology to members of the protein kinase C (PKC) family. The mouse c-akt is 90% homologous to human AKT1/RAC at the nucleic acid level and 98% homologous at the amino acid level. c-akt in the mouse is composed of 13 exons. The first exon contains a 5' untranslated GC-rich region. Since the recombination that gave rise to v-akt occurred with the 5' untranslated region, we hypothesize that the transduction of c-akt was preceded by provirus insertion upstream from or within the 5' untranslated region and in the same transcriptional orientation as the gene. c-akt was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 12 and rat chromosome 6 in close proximity to the Igh locus.

Amino Acid Sequence↗
PubMed1997

Interleukin 3-dependent survival by the Akt protein kinase.

Interleukin 3 (IL-3)-dependent survival of hematopoietic cells is known to rely on the activity of multiple signaling pathways, including a pathway leading to activation of phosphoinositide 3-kinase (PI 3-kinase), and protein kinase Akt is a direct target of PI 3-kinase. We find that Akt kinase activity is rapidly induced by the cytokine IL-3, suggesting a role for Akt in PI 3-kinase-dependent signaling in hematopoetic cells. Dominant-negative mutants of Akt specifically block Akt activation by IL-3 and interfere with IL-3-dependent proliferation. Overexpression of Akt or oncogenic v-akt protects 32D cells from apoptosis induced by IL-3 withdrawal. Apoptosis after IL-3 withdrawal is accelerated by expression of dominant-negative mutants of Akt, indicating that a functional Akt signaling pathway is necessary for cell survival mediated by the cytokine IL-3. Thus Akt appears to be an important mediator of anti-apoptotic signaling in this system.

Animals↗
PubMed1998

Stimulation of IRS-1-associated phosphatidylinositol 3-kinase and Akt/protein kinase B but not glucose transport by beta1-integrin signaling in rat adipocytes.

The signal transduction pathway by which insulin stimulates glucose transport is not understood, but a role for complexes of insulin receptor substrate (IRS) proteins and phosphatidylinositol (PI) 3-kinase as well as for Akt/protein kinase B (PKB) has been proposed. Here, we present evidence suggesting that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes. Cross-linking of beta1-integrin on the surface of rat adipocytes by anti-beta1-integrin antibody and fibronectin was found to cause greater IRS-1 tyrosine phosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activation, detected by anti-serine 473 antibody, than did 1 nM insulin. Clustering of beta1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. In contrast, beta1-integrin clustering caused neither a change in deoxyglucose transport nor an effect on the ability of insulin to stimulate deoxyglucose uptake at any concentration along the entire dose-response relationship range. The data suggest that (i) beta1-integrins can engage tyrosine kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transport in fat cells or an additional signaling pathway is required.

Adipocytes↗
PubMed1999

Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion.

The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells from a variety of apoptotic injuries. In several instances, the anti-apoptotic effect of the wild type IGF-IR is more evident under conditions of anchorage-independence than in cells in monolayer cultures. We have investigated IGF-IR signaling in cells in anoikis, a form of apoptosis that occurs when cells are denied attachment to the extra-cellular matrix. IGF-I protects mouse embryo fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival is dependent on the concentration of IGF-I and a sufficient number of functional IGF-I receptors. In this model, IGF-I protection correlates best with ras activation and cell-to-cell aggregation, while PI3-kinase, Akt and MAP kinases seem to play a lesser, alternative role.

3T3 Cells↗
PubMed1998

The activation of glycogen synthase by insulin switches from kinase inhibition to phosphatase activation during adipogenesis in 3T3-L1 cells.

The effects of insulin and platelet-derived growth factor (PDGF) on glycogen synthase activation were compared in 3T3-L1 fibroblasts and adipocytes. In the fibroblasts, PDGF elicited a stronger phosphorylation of mitogen-activated protein kinase (MAPK) and AKT than did insulin. Both agents caused a comparable stimulation of receptor autophosphorylation, MAPK, and phosphatidylinositol 3-kinase (PI3-K) activation in the adipocytes. However, adipogenesis resulted in the uncoupling of PI3-K activation by PDGF from subsequent AKT phosphorylation. The relative contributions of glycogen synthase kinase-3 (GSK-3) inactivation and protein phosphatase-1 (PP1) activation in the regulation of glycogen synthase in both cell types were evaluated. Insulin and PDGF caused a small increase in glycogen synthase a activity in the fibroblasts. Additionally, both agents caused a similar inhibition of GSK-3, while having no effect on PP1 activity. Following differentiation, insulin treatment resulted in a 5-fold stimulation of glycogen synthase, whereas PDGF was without effect. Both agents caused a comparable inhibition of GSK-3 activity in the adipocytes, whereas only insulin activated PP1. Finally, wortmannin completely blocked the stimulation of PP1 by insulin in 3T3-L1 adipocytes, indicating that PI3-K inhibition can impinge on PP1 activation. Cumulatively these results suggest that the weak activation of glycogen synthase in 3T3-L1 fibroblasts is mediated by GSK-3 inactivation, whereas in the more metabolically active adipocytes, the insulin-specific activation of glycogen synthase is mediated by PP1 activation.

3T3 Cells↗
PubMed1998

Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line.

Phosphatidylinositol (PI) 3-kinase has been suggested to mediate cell survival. Consistent with this possibility, apoptosis of conditionally (simian virus 40 Tts) immortalized rat hippocampal H19-7 neuronal cells was increased in response to wortmannin, an inhibitor of PI 3-kinase. Downstream effectors of PI 3-kinase include Rac1, protein kinase C, and the serine-threonine kinase Akt (protein kinase B). Here, we show that activation of Akt is one mechanism by which PI 3-kinase can mediate survival of H19-7 cells during serum deprivation or differentiation. While ectopic expression of wild-type Akt (c-Akt) does not significantly enhance survival in H19-7 cells, expression of activated forms of Akt (v-Akt or myristoylated Akt) results in enhanced survival which can be comparable to that conferred by Bcl-2. Conversely, expression of a dominant-negative mutant of Akt accelerates cell death upon serum deprivation or differentiation. Finally, the results indicate that Akt can transduce a survival signal for differentiating neuronal cells through a mechanism that is independent of induction of Bcl-2 or Bcl-XL or inhibition of Jun kinase activity.

Androstadienes↗
PubMed1998

Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway.

Cyclin D expression is regulated by growth factors and is necessary for the induction of mitogenesis. Herbimycin A, a drug that binds to Hsp90, induces the destruction of tyrosine kinases and causes the down-regulation of cyclin D and an Rb-dependent growth arrest in the G1 phase of the cell cycle. We find that the induction of D-cyclin expression by serum and its repression by herbimycin A are regulated at the level of mRNA translation. Induction of cyclin D by serum occurs prior to the induction of its mRNA and does not require transcription. Herbimycin A repression is characterized by a decrease in the synthetic rate of D-cyclins prior to changes in mRNA expression and in the absence of changes in the half-life of the protein. This effect on D-cyclin translation is mediated via a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. PI 3-kinase inhibitors such as wortmannin and LY294002, and rapamycin, an inhibitor of FRAP/TOR, cause a decline in the level of D-cyclins, whereas inhibitors of mitogen-activated protein kinase kinase and farnesyltransferase do not. Cells expressing the activated, myristoylated form of Akt kinase, a target of PI 3-kinase, are refractory to the effects of herbimycin A or serum starvation on D-cyclin expression. These data suggest that serum induction of cyclin D expression results from enhanced translation of its mRNA and that this results from activation of a pathway that is dependent upon PI 3-kinase and Akt kinase.

Benzoquinones↗
PubMed1999

The SH2 domain-containing inositol 5'-phosphatase (SHIP) recruits the p85 subunit of phosphoinositide 3-kinase during FcgammaRIIb1-mediated inhibition of B cell receptor signaling.

Coligation of FcgammaRIIb1 with the B cell receptor (BCR) or FcepsilonRI on mast cells inhibits B cell or mast cell activation. Activity of the inositol phosphatase SHIP is required for this negative signal. In vitro, SHIP catalyzes the conversion of the phosphoinositide 3-kinase (PI3K) product phosphatidylinositol 3,4, 5-trisphosphate (PIP3) into phosphatidylinositol 3,4-bisphosphate. Recent data demonstrate that coligation of FcgammaRIIb1 with BCR inhibits PIP3-dependent Btk (Bruton's tyrosine kinase) activation and the Btk-dependent generation of inositol trisphosphate that regulates sustained calcium influx. In this study, we provide evidence that coligation of FcgammaRIIb1 with BCR induces binding of PI3K to SHIP. This interaction is mediated by the binding of the SH2 domains of the p85 subunit of PI3K to a tyrosine-based motif in the C-terminal region of SHIP. Furthermore, the generation of phosphatidylinositol 3,4-bisphosphate was only partially reduced during coligation of BCR with FcgammaRIIb1 despite a drastic reduction in PIP3. In contrast to the complete inhibition of Tec kinase-dependent calcium signaling, activation of the serine/threonine kinase Akt was partially preserved during BCR and FcgammaRIIb1 coligation. The association of PI3K with SHIP may serve to activate PI3K and to regulate downstream events such as B cell activation-induced apoptosis.

3T3 Cells↗
PubMed1995

Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction.

A serine/threonine kinase, named protein kinase B (PKB) for its sequence homology to both protein kinase A and C, has previously been isolated. PKB, which is identical to the kinase Rac, was later found to be the cellular homologue of the transforming v-Akt. Here we show that PKB is activated by stimuli such as insulin, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Activation of PKB was inhibited by the phosphatidylinositol-3-OH kinase (PI(3)K) inhibitor wortmannin and by coexpression of a dominant-negative mutant of PI(3)K. PDGF receptor mutants that lack detectable associated PI(3)K activity also fail to induce PKB activation, PKB kinase activity is correlated with phosphorylation of PKB on serine. Finally, we show that a constructed Gag-PKB fusion protein, homologous to the v-akt oncogene, displays significantly increased ligand-independent kinase activity. Furthermore, this activity is sufficient to activate the p70 S6-kinase (p70S6K). These results suggest a role for PKB in PI(3)K-mediated signal transduction.

3T3 Cells↗
PubMed1995

Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas.

The AKT2 gene is one of the human homologues of v-akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, which codes for a serine-threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large-scale, multicenter study of AKT2 alterations in ovarian and breast cancer. Southern-blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern-blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto-oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness.

Adenocarcinoma↗