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K-Ras Mediated Murine Epidermal Tumorigenesis Is Dependent upon and Associated with Elevated Rac1 Activity

Figure 2

Increased survival of LSL-K-Ras^G12D;K14-Cre:ER mice lacking a Rac1 allele.

(A) Macroscopic view of oral papillomas from LSL-K-Ras^G12D;K14-Cre:ER (upper panel) and LSL-K-Ras^G12D;K14-Cre:ER;Rac1^Wt/- mice (lower panel). Deficiency for one Rac1 allele dramatically reduced papilloma growth. (B) Kaplan-Meier survival curve of Rac^Wt/- (n = 20), LSL-K-Ras^G12D;K14-Cre:ER (n = 78) and LSL-K-Ras^G12D;K14-Cre:ER;Rac1^Wt/- (n = 22) mice shows the dramatic difference between the two mouse strains. Median survival for LSL-K-Ras^G12D;K14-Cre:ER;Rac1^Wt/- mice was determined to be 75 days, which is 50% greater than the 51 day survival time of LSL-K-Ras^G12D;K14-Cre:ER mice. (C) Staining for the marker of cell proliferation Ki-67 revealed markedly lower levels in tumors from LSL-K-Ras^G12D;K14-Cre:ER;Rac1^Wt/- mice relative to tumors from LSL-K-Ras^G12D;K14-Cre:ER⁺ mice.

doi: https://doi.org/10.1371/journal.pone.0017143.g002