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The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis.

Rac1b, an alternative splice form of Rac1, has been previously shown to be upregulated in colon and breast cancer cells, suggesting an oncogenic role for Rac1b in these cancers. Our analysis of NSCLC tumor and matched normal tissue samples indicates Rac1b is upregulated in a significant fraction of lung tumors in correlation with mutational status of K-ras. To directly assess the oncogenic potential of Rac1b in vivo, we employed a mouse model of lung adenocarcinoma, in which the expression of Rac1b can be conditionally activated specifically in the lung. Although expression of Rac1b alone is insufficient to drive tumor initiation, the expression of Rac1b synergizes with an oncogenic allele of K-ras resulting in increased cellular proliferation and accelerated tumor growth. Finally, we show that in contrast to our previous findings demonstrating a requirement for Rac1 in K-ras-driven cell proliferation, Rac1b is not required in this context. Given the partially overlapping spectrum of downstream effectors regulated by Rac1 and Rac1b, our findings further delineate the signaling pathways downstream of Rac1 that are required for K-ras driven tumorigenesis.

Pubmed ID: 22430205


  • Zhou C
  • Licciulli S
  • Avila JL
  • Cho M
  • Troutman S
  • Jiang P
  • Kossenkov AV
  • Showe LC
  • Liu Q
  • Vachani A
  • Albelda SM
  • Kissil JL



Publication Data

February 14, 2013

Associated Grants

  • Agency: NCI NIH HHS, Id: CA124495
  • Agency: NCI NIH HHS, Id: P30 CA010815
  • Agency: NCI NIH HHS, Id: R01 CA124495
  • Agency: NCI NIH HHS, Id: R01 CA124495-04
  • Agency: NCRR NIH HHS, Id: S10 RR024693

Mesh Terms

  • Adenocarcinoma
  • Animals
  • Carcinoma, Non-Small-Cell Lung
  • Cell Transformation, Neoplastic
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Lung Neoplasms
  • Mice
  • Mice, Transgenic
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Tumor Cells, Cultured
  • rac1 GTP-Binding Protein
  • ras Proteins