Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- mice.
Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- mice.
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DOI：
10.1158/1940-6207.capr-10-0088
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Hilakivi-Clarke L
中科院分区：
文献类型：
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作者：
Yu W;Cline M;Maxwell LG;Berrigan D;Rodriguez G;Warri A;Hilakivi-Clarke L
The possibility that dietary VD3 exposure inhibits endometrial carcinogenesis in an animal model, and modifies the enhanced risk of endometrial carcinoma associated with obesity was investigated. When 4 weeks of age, Pten+/− and wildtype mice were each divided into four treatment groups and fed AIN93G control diet, or AIN93G based diet containing either 25K IU of VD3/kg diet, 58% fat to induce obesity (high fat), or high fat and 25K IU of VD3/kg diet. Mice were kept on these diets until they were sacrificed at week 28. Although VD3 did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial lesions. Specifically, high fat diet increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet fed Pten+/− mice to 78% in obese mice. Dietary VD3 decreased the incidence of endometrial pathology in obese Pten+/− mice to 25% (p<0.001). VD3 altered the endometrial expression of 25-hydroxylase (25-OHase), 1α-OHase and vitamin D receptor in the wildtype and Pten+/− mice. Estrogen receptor (ER) -α mRNA levels were higher (p<0.014) and progesterone receptor (PR) protein levels in the luminal epithelium were lower (p<0.04) in the endometrium of control diet fed Pten+/− than wildtype mice, but the expression of these receptors was not affected by the dietary exposures. VD3 reversed the obesity induced increase in osteopontin (p<0.001) and significantly increased E-cadherin expression (p<0.019) in the endometrium of obese in Pten+/− mice. Our data confirm the known association between obesity and endometrial cancer risk. Dietary exposure to VD3 inhibited the carcinogenic effect of obesity on the endometrium; this protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin.
