Mammary tumorigenesis in ApcMin/+ mice is enhanced by X irradiation with a characteristic age dependence.
The Apc(Min/+) (Min) mouse is genetically predisposed to both intestinal and mammary tumorigenesis. We investigated age-related changes in the susceptibility of mice (before, during and after puberty) to radiation-induced mammary tumorigenesis using this model. Female Min and wild-type mice having the C57BL/6J background were irradiated with 2 Gy of X rays at 2, 5, 7 and 10 weeks and killed humanely at 18 weeks of age. Min mice irradiated at 7-10 weeks of age (after puberty) developed mammary tumors with squamous metaplasia, whereas their wild-type littermates did not. Interestingly, irradiation of Min mice at 2-5 weeks (before and during puberty, respectively) did not induce mammary tumors but rather cystic nodules with metaplasia. The mammary tumors exhibited increased nuclear beta-catenin protein and loss of the wild-type Apc allele. Our results show that susceptibility to radiation-induced mammary tumorigenesis increases after puberty in Min mice, suggesting that the tumorigenic effect of ionizing radiation targets the lobular-alveolar progenitor cells, which increase in number with age and are controlled by beta-catenin signaling.
Imaoka
Tatsuhiko
T
Low Dose Radiation Effects Research Project, Research Center for Radiation Safety, National Institute of Radiological Sciences, Chiba, Japan. t_imaoka@nirs.go.jp
Okamoto
Mieko
M
Nishimura
Mayumi
M
Nishimura
Yukiko
Y
Ootawara
Masami
M
Kakinuma
Shizuko
S
Tokairin
Yutaka
Y
Shimada
Yoshiya
Y
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015674:Mammary Neoplasms, Animal / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014965:X-Rays / Q000009:adverse effects
D025601:Adenomatous Polyposis Coli Protein