| First Author | Mercer K | Year | 2005 |
| Journal | Cancer Res | Volume | 65 |
| Issue | 24 | Pages | 11493-500 |
| PubMed ID | 16357158 | Mgi Jnum | J:104375 |
| Mgi Id | MGI:3611724 | Doi | 10.1158/0008-5472.CAN-05-2211 |
| Citation | Mercer K, et al. (2005) Expression of endogenous oncogenic V600EB-raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts. Cancer Res 65(24):11493-500 |
| abstractText | 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. |
