Model of mouse mammary gland hyperproliferation and Hyperplasia Induced by a western‐style diet

Abstract

Mammary glands of female C57BL/6J mice were analyzed after they were fed a Western-style diet or control AIN-76A diet. The Western-style diet contained several risk factors found in human diets in geographic regions having increased risk for breast cancer: high fat and phosphate and low calcium and vitamin D. After they were fed these diets for 8, 14, and 20 weeks, mice were sacrificed, and mammary glands were removed for morphometric and radioautographic measurements. Although after the animals were fed the Western-style diet for 8 weeks the number of terminal ducts per mouse mammary gland (NTDMG) was similar in the Western-style and control diet groups, after they were fed the Western-style diet for 14 weeks (p < 0.05) and 20 weeks (p < 0.01) the NTDMG significantly increased compared with the control group. Moreover, there was a significant increase (p < 0.01) in the tritiated thymidine labeling index of mammary terminal ductal epithelial cells after 14 and 20 weeks of Western-style diet administration. Thus the Western-style diet induced increased epithelial cell proliferation and increased NTDMG in female mice when fed during young adult growth and development. The findings raise the possibility that the ingestion of a diet with Western-style fat and phosphate content and with low calcium and vitamin D may induce similar changes during the early development of the human mammary gland.

Ectopic expression of FGF-3 results in abnormal prostate and Wolffian duct development

“…The bar represents 50 mm epithelial cells counted from four pairs of prostatic lobes, 1.5% of epithelial cells in the bigenic prostates versus 0.2% cells in the monogenic controls stained positive for BrdU. This value is signi®cant as the mature prostate shows an extremely low rate of mitosis (Xue et al, 1997). Taken together, this result shows that FGF-3 is a potent growth factor that can elicit dramatic prostatic hyperplasia by excessively stimulating possibly the FGFR2iiib receptor (Mathieu et al, 1995;Thomson et al, 1997).…”

The Emerging Role of Vitamin D in Cancer Risk Reduction

“…Vitamin D also had a larger independent effect on risk of mammary carcinogenesis than high intake of fat or deficient intake of calcium (2,22,144). The effect of vitamin D on mammary carcinogenesis was particularly strong early in life, suggesting that low circulating levels of 25(OH)D in adolescence may be important contributors to later breast cancer risk (144). The roles of vitamin D, calcium, and fats may be linked (2,22,144).…”

“…Terminal ductal lobular units, the units of epithelial organization of the breast, have features that are analogous to intestinal crypts, such as a monolayer or bilayer of epithelial cells that originate at or near the base of the terminal duct and move distally toward the mouth of the duct (22), and the presence of vitamin D receptors (25,143 Occurrence of mammary tumors was reduced by four fifths in animals receiving adequate vitamin D compared with those receiving the minimal dose necessary for normal growth (2,22,144). Vitamin D also had a larger independent effect on risk of mammary carcinogenesis than high intake of fat or deficient intake of calcium (2,22,144).…”

New insights into calcium, dairy and colon cancer

“…The addition of calcium and vitamin D to the diet dramatically reduced or eliminated most of these tumors [35] . It also is of interest that this Western style diet in mice produced hyperproliferation in mammary duct epithelial cells [36] , pancreatic epithelial cells [37] and prostate cells [38] and that calcium and vitamin D suppressed such hyperproliferation. The molecular underpinnings of these observations are presently under study.…”