Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Expression of endogenous oncogenic V600EB-raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts.

Cancer research | Dec 15, 2005

http://www.ncbi.nlm.nih.gov/pubmed/16357158

Mutations of the human B-RAF gene are detected in approximately 8% of cancer samples, primarily in cutaneous melanomas (70%). The most common mutation (90%) is a valine-to-glutamic acid mutation at residue 600 (V600E; formerly V599E according to previous nomenclature). Using a Cre/Lox approach, we have generated a conditional knock-in allele of (V600E)B-raf in mice. We show that widespread expression of (V600E)B-Raf cannot be tolerated in embryonic development, with embryos dying approximately 7.5 dpc. Directed expression of mutant (V600E)B-Raf to somatic tissues using the IFN-inducible Mx1-Cre mouse strain induces a proliferative disorder and bone marrow failure with evidence of nonlymphoid neoplasia of the histiocytic type leading to death within 4 weeks of age. However, expression of mutant B-Raf does not alter the proliferation profile of all somatic tissues. In primary mouse embryonic fibroblasts, expression of endogenous (V600E)B-Raf induces morphologic transformation, increased cell proliferation, and loss of contact inhibition. Thus, (V600E)B-Raf is able to induce several hallmarks of transformation in some primary mouse cells without evidence for the involvement of a cooperating oncogene or tumor suppressor gene.

Pubmed ID: 16357158 RIS Download

Mesh terms: Animals | Apoptosis | Bone Marrow | Cell Adhesion | Cell Proliferation | Congenital Abnormalities | Embryo, Mammalian | Female | Fibroblasts | Integrases | MAP Kinase Signaling System | Male | Mice | Mice, Knockout | Mitogen-Activated Protein Kinase Kinases | Mutation | Pregnancy | Proto-Oncogene Proteins B-raf | Signal Transduction

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: Cancer Research UK, Id: A6969

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.