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      Endogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects

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          Abstract

          Activating mutations in the ras oncogene are not considered sufficient to induce abnormal cellular proliferation in the absence of cooperating oncogenes. We demonstrate that the conditional expression of an endogenous K-ras(G12D) allele in murine embryonic fibroblasts causes enhanced proliferation and partial transformation in the absence of further genetic abnormalities. Interestingly, K-ras(G12D)-expressing fibroblasts demonstrate attenuation and altered regulation of canonical Ras effector signaling pathways. Widespread expression of endogenous K-ras(G12D) is not tolerated during embryonic development, and directed expression in the lung and GI tract induces preneoplastic epithelial hyperplasias. Our results suggest that endogenous oncogenic ras is sufficient to initiate transformation by stimulating proliferation, while further genetic lesions may be necessary for progression to frank malignancy.

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          Author and article information

          Journal
          Cancer Cell
          Cancer Cell
          Elsevier BV
          15356108
          April 2004
          April 2004
          : 5
          : 4
          : 375-387
          Article
          10.1016/S1535-6108(04)00085-6
          15093544
          e6e8b586-b8db-4b4b-9476-227a5a3c9122
          © 2004

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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