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[Cancer Research 64, 7002-7010, October 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Deregulated Akt3 Activity Promotes Development of Malignant Melanoma

Jill M. Stahl1, Arati Sharma1, Mitchell Cheung1, Melissa Zimmerman1, Jin Q. Cheng4, Marcus W. Bosenberg5, Mark Kester1, Lakshman Sandirasegarane1 and Gavin P. Robertson1,2,3,6

Departments of 1 Pharmacology, 2 Pathology, and 3 Dermatology, The Pennsylvania State College of Medicine, Hershey, Pennsylvania; 4 University of South Florida College of Medicine, Tampa, Florida; 5 Department of Pathology, The University of Vermont, Burlington, Vermont; and 6 The Foreman Foundation for Melanoma Research, Hershey, Pennsylvania

Malignant melanoma is the skin cancer with the most significant impact on man, carrying the highest risk of death from metastasis. Both incidence and mortality rates continue to rise each year, with no effective long-term treatment on the horizon. In part, this reflects lack of identification of critical genes involved and specific therapies targeted to correct these defects. We report that selective activation of the Akt3 protein promotes cell survival and tumor development in 43 to 60% of nonfamilial melanomas. The predominant Akt isoform active in melanomas was identified by showing that small interfering RNA (siRNA) against only Akt3, and not Akt1 or Akt2, lowered the amount of phosphorylated (active) Akt in melanoma cells. The amount of active Akt3 increased progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Mechanisms of Akt3 deregulation occurred through a combination of overexpression of Akt3 accompanying copy number increases of the gene and decreased PTEN protein function occurring through loss or haploinsufficiency of the PTEN gene. Targeted reduction of Akt3 activity with siRNA or by expressing active PTEN protein stimulated apoptotic signaling, which reduced cell survival by increasing apoptosis rates thereby inhibiting melanoma tumor development. Identifying Akt3 as a selective target in melanoma cells provides new therapeutic opportunities for patients in the advanced stages of this disease.




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Current Perspectives on Akt Akt-ivation and Akt-ions
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[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
S. P. Fortin, M. J. Ennis, B. A. Savitch, D. Carpentieri, W. S. McDonough, J. A. Winkles, J. C. Loftus, C. Kingsley, G. Hostetter, and N. L. Tran
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[Abstract] [Full Text] [PDF]

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 DMMHome page
C. Michailidou, M. Jones, P. Walker, J. Kamarashev, A. Kelly, and A. F. L. Hurlstone
Dissecting the roles of Raf- and PI3K-signalling pathways in melanoma formation and progression in a zebrafish model
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[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. M. Roccaro, A. Sacco, B. Thompson, X. Leleu, A. K. Azab, F. Azab, J. Runnels, X. Jia, H. T. Ngo, M. R. Melhem, et al.
MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma
Blood, June 25, 2009; 113(26): 6669 - 6680.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. S.M. Smalley, K. L. Nathanson, and K. T. Flaherty
Genetic Subgrouping of Melanoma Reveals New Opportunities for Targeted Therapy
Cancer Res., April 15, 2009; 69(8): 3241 - 3244.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
B. Horst, S. K. Gruvberger-Saal, B. D. Hopkins, L. Bordone, Y. Yang, K. A. Chernoff, I. Uzoma, V. Schwipper, J. Liebau, N. J. Nowak, et al.
Gab2-Mediated Signaling Promotes Melanoma Metastasis
Am. J. Pathol., April 1, 2009; 174(4): 1524 - 1533.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Sharma, A. K. Sharma, S. V. Madhunapantula, D. Desai, S. J. Huh, P. Mosca, S. Amin, and G. P. Robertson
Targeting Akt3 Signaling in Malignant Melanoma Using Isoselenocyanates
Clin. Cancer Res., March 1, 2009; 15(5): 1674 - 1685.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. C. Jiang, Z. G. Mao, K. A. Avery-Kiejda, M. Wade, P. Hersey, and X. D. Zhang
Glucose-regulated protein 78 antagonizes cisplatin and adriamycin in human melanoma cells
Carcinogenesis, February 1, 2009; 30(2): 197 - 204.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
M. Degtyarev, A. De Maziere, C. Orr, J. Lin, B. B. Lee, J. Y. Tien, W. W. Prior, S. van Dijk, H. Wu, D. C. Gray, et al.
Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents
J. Cell Biol., October 6, 2008; 183(1): 101 - 116.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. A. Tran, R. Gowda, A. Sharma, E.-J. Park, J. Adair, M. Kester, N. B. Smith, and G. P. Robertson
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[Abstract] [Full Text] [PDF]

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S. Fedida-Metula, S. Elhyany, S. Tsory, S. Segal, M. Hershfinkel, I. Sekler, and D. Fishman
Targeting lipid rafts inhibits protein kinase B by disrupting calcium homeostasis and attenuates malignant properties of melanoma cells
Carcinogenesis, August 1, 2008; 29(8): 1546 - 1554.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Inoue-Narita, K. Hamada, T. Sasaki, S. Hatakeyama, S. Fujita, K. Kawahara, M. Sasaki, H. Kishimoto, S. Eguchi, I. Kojima, et al.
Pten Deficiency in Melanocytes Results in Resistance to Hair Graying and Susceptibility to Carcinogen-Induced Melanomagenesis
Cancer Res., July 15, 2008; 68(14): 5760 - 5768.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
A. Sekulic, P. Haluska Jr, A. J. Miller, J. G. De Lamo, S. Ejadi, J. S. Pulido, D. R. Salomao, E. C. Thorland, R. G. Vile, D. L. Swanson, et al.
Malignant Melanoma in the 21st Century: The Emerging Molecular Landscape
Mayo Clin. Proc., July 1, 2008; 83(7): 825 - 846.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. S. Lo and O. N. Witte
Transforming Growth Factor-{beta} Activation Promotes Genetic Context-Dependent Invasion of Immortalized Melanocytes
Cancer Res., June 1, 2008; 68(11): 4248 - 4257.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
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Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies
Mol. Cancer Ther., June 1, 2008; 7(6): 1347 - 1354.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. A. Tran, C. D. Smith, M. Kester, and G. P. Robertson
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Clin. Cancer Res., June 1, 2008; 14(11): 3571 - 3581.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Dhawan, Y. Su, Y. M. Thu, Y. Yu, P. Baugher, D. L. Ellis, T. Sobolik-Delmaire, M. Kelley, T. C. Cheung, C. F. Ware, et al.
The Lymphotoxin-{beta} Receptor Is an Upstream Activator of NF-{kappa}B-mediated Transcription in Melanoma Cells
J. Biol. Chem., May 30, 2008; 283(22): 15399 - 15408.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Cheung, A. Sharma, S. V. Madhunapantula, and G. P. Robertson
Akt3 and Mutant V600EB-Raf Cooperate to Promote Early Melanoma Development
Cancer Res., May 1, 2008; 68(9): 3429 - 3439.
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Home page
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Mol. Cancer Ther., May 1, 2008; 7(5): 1297 - 1308.
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Home page
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Mol. Cancer Ther., August 1, 2007; 6(8): 2139 - 2148.
[Abstract] [Full Text] [PDF]

Home page
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Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1330 - 1340.
[Abstract] [Full Text] [PDF]

Home page
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Targeting Mutant (V600E) B-Raf in Melanoma Interrupts Immunoediting of Leukocyte Functions and Melanoma Extravasation
Cancer Res., June 15, 2007; 67(12): 5814 - 5820.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
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J. Clin. Oncol., April 20, 2007; 25(12): 1606 - 1620.
[Abstract] [Full Text] [PDF]

Home page
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Cancer Res., April 15, 2007; 67(8): 3626 - 3636.
[Abstract] [Full Text] [PDF]

Home page
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B. Stecca, C. Mas, V. Clement, M. Zbinden, R. Correa, V. Piguet, F. Beermann, and A. Ruiz i Altaba
Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways
PNAS, April 3, 2007; 104(14): 5895 - 5900.
[Abstract] [Full Text] [PDF]

Home page
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K. S.M. Smalley, R. Contractor, N. K. Haass, A. N. Kulp, G. E. Atilla-Gokcumen, D. S. Williams, H. Bregman, K. T. Flaherty, M. S. Soengas, E. Meggers, et al.
An Organometallic Protein Kinase Inhibitor Pharmacologically Activates p53 and Induces Apoptosis in Human Melanoma Cells
Cancer Res., January 1, 2007; 67(1): 209 - 217.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. E. Cristiano, J. C. Chan, K. M. Hannan, N. A. Lundie, N. J. Marmy-Conus, I. G. Campbell, W. A. Phillips, M. Robbie, R. D. Hannan, and R. B. Pearson
A Specific Role for AKT3 in the Genesis of Ovarian Cancer through Modulation of G2-M Phase Transition
Cancer Res., December 15, 2006; 66(24): 11718 - 11725.
[Abstract] [Full Text] [PDF]

Home page
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B. Bedogni, S. M. Welford, A. C. Kwan, J. Ranger-Moore, K. Saboda, and M. B. Powell
Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase kinase 1/2 prevents melanoma development and promotes melanoma regression in the transgenic TPRas mouse model
Mol. Cancer Ther., December 1, 2006; 5(12): 3071 - 3077.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. Blazquez, A. Carracedo, L. Barrado, P. J. Real, J. L. Fernandez-Luna, G. Velasco, M. Malumbres, and M. Guzman
Cannabinoid receptors as novel targets for the treatment of melanoma
FASEB J, December 1, 2006; 20(14): 2633 - 2635.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L. Heron-Milhavet, C. Franckhauser, V. Rana, C. Berthenet, D. Fisher, B. A. Hemmings, A. Fernandez, and N. J. C. Lamb
Only Akt1 Is Required for Proliferation, while Akt2 Promotes Cell Cycle Exit through p21 Binding
Mol. Cell. Biol., November 15, 2006; 26(22): 8267 - 8280.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. M. Karst, D. L. Dai, J. Q. Cheng, and G. Li
Role of p53 Up-regulated Modulator of Apoptosis and Phosphorylated Akt in Melanoma Cell Growth, Apoptosis, and Patient Survival.
Cancer Res., September 15, 2006; 66(18): 9221 - 9226.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. S. Spofford, E. V. Abel, K. Boisvert-Adamo, and A. E. Aplin
Cyclin D3 Expression in Melanoma Cells Is Regulated by Adhesion-dependent Phosphatidylinositol 3-Kinase Signaling and Contributes to G1-S Progression
J. Biol. Chem., September 1, 2006; 281(35): 25644 - 25651.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Sharma, M. A. Tran, S. Liang, A. K. Sharma, S. Amin, C. D. Smith, C. Dong, and G. P. Robertson
Targeting Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases
Cancer Res., August 15, 2006; 66(16): 8200 - 8209.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
L. Chin, L. A. Garraway, and D. E. Fisher
Malignant melanoma: genetics and therapeutics in the genomic era.
Genes & Dev., August 15, 2006; 20(16): 2149 - 2182.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Saldanha, L. Potter, P. DaForno, and J. H. Pringle
Cutaneous Melanoma Subtypes Show Different BRAF and NRAS Mutation Frequencies
Clin. Cancer Res., August 1, 2006; 12(15): 4499 - 4505.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Funes, J. K. Miller, C. Lai, K. L. Carraway III, and C. Sweeney
The Mucin Muc4 Potentiates Neuregulin Signaling by Increasing the Cell-surface Populations of ErbB2 and ErbB3
J. Biol. Chem., July 14, 2006; 281(28): 19310 - 19319.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
A. J. Miller and M. C. Mihm Jr.
Melanoma.
N. Engl. J. Med., July 6, 2006; 355(1): 51 - 65.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Mirmohammadsadegh, A. Marini, S. Nambiar, M. Hassan, A. Tannapfel, T. Ruzicka, and U. R. Hengge
Epigenetic Silencing of the PTEN Gene in Melanoma.
Cancer Res., July 1, 2006; 66(13): 6546 - 6552.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
K. S.M. Smalley, N. K. Haass, P. A. Brafford, M. Lioni, K. T. Flaherty, and M. Herlyn
Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases
Mol. Cancer Ther., May 1, 2006; 5(5): 1136 - 1144.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. T. Flaherty
Chemotherapy and targeted therapy combinations in advanced melanoma.
Clin. Cancer Res., April 1, 2006; 12(7): 2366s - 2370s.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
C Festuccia, P Muzi, D Millimaggi, L Biordi, G L Gravina, S Speca, A Angelucci, V Dolo, C Vicentini, and M Bologna
Molecular aspects of gefitinib antiproliferative and pro-apoptotic effects in PTEN-positive and PTEN-negative prostate cancer cell lines
Endocr. Relat. Cancer, December 1, 2005; 12(4): 983 - 998.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Takeuchi, J. Kim, A. Fujimoto, N. Umetani, T. Mori, A. Bilchik, R. Turner, A. Tran, C. Kuo, and D. S.B. Hoon
X-Linked Inhibitor of Apoptosis Protein Expression Level in Colorectal Cancer Is Regulated by Hepatocyte Growth Factor/C-Met Pathway via Akt Signaling
Clin. Cancer Res., November 1, 2005; 11(21): 7621 - 7628.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Bloethner, B. Chen, K. Hemminki, J. Muller-Berghaus, S. Ugurel, D. Schadendorf, and R. Kumar
Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines
Carcinogenesis, July 1, 2005; 26(7): 1224 - 1232.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Sharma, N. R. Trivedi, M. A. Zimmerman, D. A. Tuveson, C. D. Smith, and G. P. Robertson
Mutant V599EB-Raf Regulates Growth and Vascular Development of Malignant Melanoma Tumors
Cancer Res., March 15, 2005; 65(6): 2412 - 2421.
[Abstract] [Full Text] [PDF]


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