Hilakivi-Clarke L, Stoica A, Raygada M, Martin M B
Lombardi Cancer Center, Department of Psychiatry, Georgetown University, Washington, DC 20007, USA.
Cancer Res. 1998 Feb 15;58(4):654-60.
Previous studies have shown that a diet high in polyunsaturated fatty acids increases mammary tumor incidence in adult and pregnant mice and rats and in the female offspring. The present study investigated whether a high-fat diet alters the number of estrogen receptor (ER) binding sites and protein kinase C (PKC) activity in the mammary gland of these animals. In the female offspring, the effects of maternal exposure to a high-fat diet during pregnancy on development of the mammary epithelial tree were studied also. BALB/c mice were kept on a diet containing either 43% (high-fat) or 16% (low-fat) calories from corn oil, which consists mostly of n-6 polyunsaturated fatty acids, for 1 month. In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice. In pregnant mice, a high-fat diet increased ER binding sites by 61% and PKC activity by 51%. In contrast to adult and pregnant mice, females exposed to a high-fat diet only in utero through their pregnant mother exhibited a significantly reduced number of mammary ER binding sites by age 45 days (78% decrease) and a reduction in PKC activity by ages 30 and 100 days (44 and 20% decrease, respectively). The mammary epithelial tree of the high-fat offspring contained more terminal end buds and was less differentiated than that of the low-fat offspring. These findings show that consumption of a high-fat diet increases ER and PKC in the adult and pregnant mouse mammary gland, perhaps contributing to the fat-induced promotion of mammary tumorigenesis. In contrast, reduced ER and PKC following a high-fat exposure in utero may be associated with increased susceptibility to carcinogenesis, possibly due to an increased number of terminal end buds that are the sites of neoplastic transformation in the mammary gland.
以往的研究表明，富含多不饱和脂肪酸的饮食会增加成年和怀孕小鼠、大鼠以及雌性后代的乳腺肿瘤发生率。本研究调查了高脂饮食是否会改变这些动物乳腺中雌激素受体（ER）结合位点的数量和蛋白激酶C（PKC）的活性。在雌性后代中，还研究了母体在怀孕期间接触高脂饮食对乳腺上皮树发育的影响。将BALB/c小鼠分别喂食含43%（高脂）或16%（低脂）玉米油热量的饮食1个月，玉米油主要由n-6多不饱和脂肪酸组成。与低脂小鼠相比，成年雌性高脂小鼠乳腺中的ER结合位点数量增加了6倍，PKC活性增加了2倍。在怀孕小鼠中，高脂饮食使ER结合位点增加了61%，PKC活性增加了51%。与成年和怀孕小鼠不同，仅在子宫内通过怀孕母亲接触高脂饮食的雌性小鼠，到45日龄时乳腺ER结合位点数量显著减少（减少78%），到30日龄和100日龄时PKC活性降低（分别降低44%和20%）。高脂后代的乳腺上皮树比低脂后代含有更多的终末芽，且分化程度更低。这些发现表明，食用高脂饮食会增加成年和怀孕小鼠乳腺中的ER和PKC，这可能有助于脂肪诱导的乳腺肿瘤发生促进作用。相比之下，子宫内接触高脂饮食后ER和PKC减少可能与致癌易感性增加有关，这可能是由于终末芽数量增加，而终末芽是乳腺肿瘤转化的部位。
