Overexpression of Akt converts radial growth melanoma to vertical growth melanoma.

Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Research Abstract Details 

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Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Abstract Text:

Baskaran Govindarajan,James E Sligh,Bethaney J Vincent,Meiling Li,Jeffrey A Canter,Brian J Nickoloff,Richard J Rodenburg,Jan A Smeitink,Larry Oberley,Yuping Zhang,Joyce Slingerland,Rebecca S Arnold,J David Lambeth,Cynthia Cohen,Lu Hilenski,Kathy Griendling,Marta , Cuezva,Jack L Arbiser,

Melanoma is the cancer with the highest increase in incidence, and transformation of radial growth to vertical growth (i.e., noninvasive to invasive) melanoma is required for invasive disease and metastasis. We have previously shown that p42/p44 MAP kinase is activated in radial growth melanoma, suggesting that further signaling events are required for vertical growth melanoma. The molecular events that accompany this transformation are not well understood. Akt, a signaling molecule downstream of PI3K, was introduced into the radial growth WM35 melanoma in order to test whether Akt overexpression is sufficient to accomplish this transformation. Overexpression of Akt led to upregulation of VEGF, increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism. Subcutaneous implantation of WM35 cells overexpressing Akt led to rapidly growing tumors in vivo, while vector control cells did not form tumors. We demonstrated that Akt was associated with malignant transformation of melanoma through at least 2 mechanisms. First, Akt may stabilize cells with extensive mitochondrial DNA mutation, which can generate ROS. Second, Akt can induce expression of the ROS-generating enzyme NOX4. Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma.

Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Publishing Authors By Initials

B Govindarajan,JE Sligh,BJ Vincent,M Li,JA Canter,BJ Nickoloff,RJ Rodenburg,JA Smeitink,L Oberley,Y Zhang,J Slingerland,RS Arnold,JD Lambeth,C Cohen,L Hilenski,K Griendling,M ,JM Cuezva,JL Arbiser,

For similar peptides: intercellular signaling peptides and proteins: angiogenic proteins: vascular endothelial growth factors: vascular endothelial growth factor a research abstracts see: peptides: intercellular signaling peptides and proteins: angiogenic proteins: vascular endothelial growth factors: vascular endothelial growth factor a research

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Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 719-29

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 22

MONTH: 02

YEAR: 2007

Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Keywords Mesh Terms:

KEYWORDS: Vascular Endothelial Growth Factor A

MESH TERMS: metabolism

Chemical & Substance for Abstract: Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Overexpression of Akt converts radial growth melanoma to vertical growth melanoma.

AFFILIATION: Department of Dermatology, Emory University School of Medicine, and Atlanta Veterans Administration Medical Center, Atlanta, Georgia 30322, USA.

Country: United States

AGENCY: United States NIAMS

GRANT: R01 AR02030

ACRONYM: AR

MEDLINETA: J Clin Invest

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