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 [
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Figure 3Histopathologic and molecular characterization of lesions in
beclin 1+/– mice. (
a–
c) Representative well-differentiated papillary lung carcinoma in a
beclin 1+/– mouse, stained with H&E (
a), anti–Beclin 1 (
b), or anti–TTF-1 (
c). The inset in
a shows lungs with subpleural tumor nodules (arrows). Beclin 1 immunoreactivity levels similar to those shown in
b were observed in all lung carcinomas in
beclin 1+/– mice (
n = 10; data not shown). (
d and
e) Representative well-differentiated hepatocellular carcinoma in a
beclin 1+/– mouse, stained with H&E (
d) or anti–Beclin 1 (
e). The inset in
d shows gross pathology of liver tumor. Beclin 1 immunoreactivity levels similar to those shown in
e were observed in all hepatocellular carcinomas identified in
beclin 1+/– mice (
n = 4; data not shown). (
f) Representative area of preneoplastic small-cell dysplasia in the liver of a
beclin 1+/– mouse that transgenically expresses the HBV large-envelope polypeptide. (
g–
i) Representative DLCL in a
beclin 1+/– mouse, stained with H&E (
g), anti-Pax5 (dark purple) and anti-CD3 (brown;
h), and anti–BCL-6 (
i). The inset in
g shows lymphoma (arrow) adjacent to normal kidney. (
j) Example of lymphoproliferative disease in the thymus of a
beclin 1+/– mouse with medullary follicular hyperplasia and cortical effacement. The arrow denotes a germinal center. (
k) Southern blot analysis to detect the wild-type and disrupted
beclin 1 allele in tumor samples and matched normal tissue. No evidence of allelic loss is seen in
beclin 1+/– tumors. Data are shown for one example of each of the three types of malignancy observed. Similar findings were observed for all palpable malignancies (
n = 15). Scale bars:
a–
i, 50 μm;
j, 1 mm.
