Figure 1.

Enforced Expression of CDK6 in p185^BCR-ABL-Transformed Cells Unmasks Its Tumor-Suppressing Activity

(A) ³[H]-thymidine incorporation of Cdk6^+/+ (expressing a pMSCV-puro-based retrovirus) and Cdk6^+/++Cdk6 (expressing a pMSCV-Cdk6-puro-based retrovirus) p185^BCR-ABL-transformed cells (n = 4; ^∗∗p = 0.009).

(B) Colony-forming assays were performed by seeding a defined number of p185^BCR-ABL-transformed Cdk6^+/+ or Cdk6^+/++Cdk6 cells in growth factor-free methylcellulose. Left side: representative set of pictures. Right side: number of colonies per dish after incubation for 5 days (n = 4/genotype; ^∗p = 0.023).

(C) Kaplan-Meier plot of Nu/Nu mice injected subcutaneously with Cdk6^+/+ or Cdk6^+/++Cdk6 cells (n = 4 cell lines/genotype; n = 2 mice/cell line; mean survival: 18 [Cdk6^+/+] versus 26 [Cdk6^+/++Cdk6] days; ^∗∗p = 0.002).

(D) Kaplan-Meier plot of Rag2^−/− mice transplanted intravenously with Cdk6^+/+ or Cdk6^+/++Cdk6 cells (n = 3 cell lines/genotype; n = 6 mice/genotype; mean survival: 18 [Cdk6^+/+] and 29 [Cdk6^+/++Cdk6] days; ^∗p = 0.014).

(E and F) Immunohistochemical stainings for the proliferation marker Ki-67 of Cdk6^+/+ (n = 4) and Cdk6^+/++Cdk6 (n = 9) tumors were quantified with HistoQuest software. A representative set of pictures is given (E). Original magnification 20×. Bar graphs depict percentage of Ki-67-positive tumor cells (F; p = 0.029 [^∗]).

Error bars indicate the mean ± SEM. See also Figure S1.