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.

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. Research Abstract Details 

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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. Abstract Text:

Barbara Bedogni,Scott M Welford,Andrea C Kwan,James Ranger-Moore,Kathylynn Saboda,Marianne Broome Powell,

A number of human melanomas show hyperactivation of the Ras pathway due to mutations of the molecule or alteration of upstream or downstream effectors. In this study, we evaluated the effect of blocking the two Ras downstream pathways phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase on melanoma development and regression in the TPRas mouse model. The inhibition of these two signaling cascades by topically applied Ly294002 and U0126 significantly delayed melanoma development and significantly decreased the tumor incidence, particularly when the drugs were applied in combination. Treatment with the inhibitors of established melanomas resulted in complete remission in 33% of mice and partial regression in 46% of mice when drugs were delivered in combination. These responses correlated with increased apoptosis and decreased proliferation both in vitro and in vivo and reduced tumor angiogenesis. In conclusion, this study strongly supports the role of the phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways in the development and maintenance of Ras-dependent melanomas and supports the notion that specific inhibition of these effectors may represent a very promising avenue for the treatment and prevention of the disease.

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. Publishing Authors By Initials

B Bedogni,SM Welford,AC Kwan,J Ranger-Moore,K Saboda,MB Powell,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: map kinase kinase kinases: raf kinases research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: map kinase kinase kinases: raf kinases research

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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. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular cancer therapeutics

VOLUME: 5

Page Numbers: 3071-7

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 3

MONTH: Dec

YEAR: 2006

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. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101132535

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. Keywords Mesh Terms:

KEYWORDS: raf Kinases

MESH TERMS: metabolism

Chemical & Substance for Abstract: 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. Information

Substance Name: raf Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for 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.

AFFILIATION: Division of Radiation and Cancer Biology, 269 Campus Drive, CCSR-S-1230, Stanford 94305, CA, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA27502

ACRONYM: CA

MEDLINETA: Mol Cancer Ther

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