Histological Findings of Mammary Gland Development and Risk of Breast Cancer in Mutant Mouse Models.

PURPOSE

The breast cancer susceptibility gene, , is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in mutant mice.

METHODS

Five mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. In another experiment, 15 mutant mice were followed up to 8 months after birth and classified into tumor-bearing (11 mice) and tumor-free (4 mice) groups. Excised mammary gland tissues were stained with Carmine Alum, and the number of terminal end buds (or alveolar buds), branching density, and duct elongation were measured using image analysis programs. Differences between the two groups were assessed using paired -test.

RESULTS

One-month-old mutant mice showed a higher number of terminal end buds (23.8 ± 1.0 vs. 15.6 ± 0.8, = 0.0002), branching density (11.7 ± 0.4 vs. 9.6 ± 0.5%, = 0.0082), and duct elongation (9.7 ± 0.7 vs. 7.3 ± 0.4 mm, = 0.0186) than controls. However, there was no difference between the 3- and 8-month-old groups. In mutant mice, the tumor-bearing group showed a significantly higher number of alveolar buds (142.7 ± 5.5 vs. 105.5 ± 5.4, = 0.0008) and branching density (30.0 ± 1.0 vs. 24.1 ± 1.1%, = 0.008) than the tumor-free group; however, duct elongation was not different (23.9 ± 0.6 vs. 23.6 ± 0.6 mm, = 0.8099) between the groups.

CONCLUSION

mutant mice exhibited early pubertal mammary gland development and delayed age-related mammary gland involution was associated with breast cancer. Our results may have clinical implications for predicting breast cancer risk and developing prevention strategies for mutation carriers.