Mammary tumorigenesis in ApcMin/+ mice is enhanced by X irradiation with a characteristic age dependence.

Abstract

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.

• Authors: Tatsuhiko Imaoka, Mieko Okamoto, Mayumi Nishimura, Yukiko Nishimura, Masami Ootawara, Shizuko Kakinuma, Yutaka Tokairin, Yoshiya Shimada
• Journal: Radiation research (Radiat Res) Vol. 165 Issue 2 Pg. 165-73 (Feb 2006) ISSN: 0033-7587 [Print] United States
• PMID: 16435915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenomatous Polyposis Coli Protein

Topics

• Adenomatous Polyposis Coli Protein (genetics, metabolism)
• Aging (genetics, metabolism, pathology, radiation effects)
• Animals
• Genetic Predisposition to Disease (genetics)
• Mammary Neoplasms, Animal (etiology, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasms, Radiation-Induced (genetics, metabolism, pathology)
• X-Rays (adverse effects)