Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
J. Clin. Invest. Xueping Qu, et al. 112:1809 doi:10.1172/JCI20039 [Go to this article.]

Figure 2
Increase in the frequency of spontaneous malignancies (a–g) and accelerated development of HBV-induced premalignant lesions in beclin 1 heterozygous-deficient mice (h). (a and b) Kaplan-Meier plot of time to development of macroscopic malignancy (a) and any malignancy (b) in beclin 1^+/– (solid lines, filled circles) versus beclin 1^+/+ (dotted lines, open circles) mice (P < 0.0001, log-rank test). “Macroscopic malignancy” refers to tumors observed upon gross inspection that were subsequently confirmed to be malignancies upon histologic examination. “Any malignancy” denotes either a macroscopic or a microscopic malignancy detected upon complete histologic survey of all major internal organs. (c–g) Prevalence of macroscopic malignancies (c), all malignancies (d), lung carcinomas (e), hepatocellular carcinomas (f), and lymphomas and lymphoproliferative disease (LPD; g) in beclin 1^+/– (black bars) versus beclin 1^+/+ (white bars) mice (P < 0.0001, Fisher’s exact test for c–g). In g, black denotes lymphoma and gray denotes lymphoproliferative disease. (h) Extent of small-cell dysplasia in livers from 13-month-old beclin 1^+/– (n = 27; black bars) versus beclin 1^+/+ (n = 32; white bars) HBV transgenic mice. The scale for small-cell dysplasia (72) is: 0, absent or rare foci; 1+, <25% of liver with small-cell dysplasia; 2+, 25–50% of liver with small-cell dysplasia; 3+, >50% of liver with small-cell dysplasia. Beclin 1^+/– HBV transgenic mice have significantly more severe disease (P = 0.0289, Mantel-Haenszel χ² test).