Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth.

Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Research Abstract Details 

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Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Abstract Text:

Honglin Hao,Vanessa M Muniz-Medina,Heena Mehta,Nancy E Thomas,Vladimir Khazak,Channing J Der,Janiel M Shields,

Mutational activation of Ras and a key downstream effector of Ras, the B-Raf serine/threonine kinase, has been observed in melanomas and colorectal carcinomas. These observations suggest that inhibition of B-Raf activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) and the extracellular signal-regulated kinase MAPK cascade may be an effective approach for the treatment of RAS and B-RAF mutation-positive melanomas and colon carcinomas. Although recent studies with interfering RNA (RNAi) and pharmacologic inhibitors support a critical role for B-Raf signaling in melanoma growth, whether mutant B-Raf has an equivalent role in promoting colorectal carcinoma growth has not been determined. In the present study, we used both RNAi and pharmacologic approaches to further assess the role of B-Raf activation in the growth of human melanomas and additionally determined if a similar role for mutant B-Raf is seen for colorectal carcinoma cell lines. We observed that RNAi suppression of mutant B-Raf(V600E) expression strongly suppressed the anchorage-dependent growth of B-RAF mutation-positive melanoma, but not colorectal carcinoma, cells. However, the anchorage-independent and tumorigenic growth of B-RAF mutation-positive colorectal carcinomas was dependent on mutant B-Raf function. Finally, pharmacologic inhibition of MEK and Raf was highly effective at inhibiting the growth of B-RAF mutation-positive melanomas and colorectal carcinoma cells, whereas inhibitors of other protein kinases activated by Ras (AKT, c-Jun NH(2)-terminal kinase, and p38 MAPK) were less effective. Our observations suggest that Raf and MEK inhibitors may be effective for the treatment of B-RAF mutation-positive colorectal carcinomas as well as melanomas.

Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Publishing Authors By Initials

H Hao,VM Muniz-Medina,H Mehta,NE Thomas,V Khazak,CJ Der,JM Shields,

For similar neoplasms: neoplasms by site: skin neoplasms research abstracts see: neoplasms: neoplasms by site: skin neoplasms research

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Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Journal Published:

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

Journal: Molecular cancer therapeutics

VOLUME: 6

Page Numbers: 2220-9

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 3

MONTH: Aug

YEAR: 2007

Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101132535

Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Keywords Mesh Terms:

KEYWORDS: Skin Neoplasms

MESH TERMS: pathology

Chemical & Substance for Abstract: Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth. Information

Substance Name: Proto-Oncogene Proteins B-raf

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Context-dependent roles of mutant B-Raf signaling in melanoma and colorectal carcinoma cell growth.

AFFILIATION: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC 27599-7295, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA69577

ACRONYM: CA

MEDLINETA: Mol Cancer Ther

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