High birth weight increases mammary tumorigenesis in rats
High birth weight increases mammary tumorigenesis in rats
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DOI：
10.1002/ijc.21936
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发表时间：
2006-10-01
影响因子：
6.4
通讯作者：
Hilakivi-Clarke, Leena
中科院分区：
文献类型：
--
作者：
de Assis, Sonia;Khan, Galam;Hilakivi-Clarke, Leena
流行病学研究调查了高出生体重是否与乳腺癌风险增加有关，但结果仍然不确定。本研究旨在确定高出生体重是否会增加动物模型中致癌物诱导的乳腺肿瘤发生的后期易感性，并确定介导这种关联的机制。妊娠雌性Sprague道利大鼠在妊娠期间喂食对照或高脂饮食。母亲暴露于高脂肪饮食增加了妊娠瘦素水平和后代的出生体重，但对妊娠雌二醇或胰岛素样生长因子1水平没有影响。评估后代乳腺形态学和蛋白质表达的变化。高出生体重子代的乳腺上皮树更致密，包含更多的终末芽，并表现出更多的增殖细胞。此外，他们的乳腺表达较低水平的ER-α，但较高水平的活化MAPK。未观察到细胞凋亡的变化。高出生体重的大鼠在7，12-二甲基苯并[a]蒽诱导的乳腺肿瘤发生明显更早，并且肿瘤比对照组更大。与对照组相比，该组肿瘤表达更高水平的瘦素受体和激活的Akt，并且包含更少的凋亡细胞。我们的研究结果表明，高出生体重与乳腺肿瘤发生的潜伏期缩短有关，这可能反映了活化MAPK水平的增加和肿瘤生长的增加，这可能是由于肿瘤中瘦素受体和活化Akt水平较高导致的凋亡反应较低所致。(c)2006威利-利斯公司
Epidemiological studies have investigated whether a high birth weight is associated with increased breast cancer risk, but the results remain inconclusive. This study was designed to determine whether high birth weight increases later susceptibility to carcinogen-induced mammary tumorigenesis in an animal model and to determine mechanisms mediating this association. Pregnant female Sprague Dawley rats were fed either a control or a high-fat diet during the extent of gestation. Maternal exposure to the high-fat diet increased pregnancy leptin levels and offspring's birth weight, but had no effect on pregnancy estradiol or insulin-like growth factor 1 levels. Changes in the offspring's mammary gland morphology and protein expression were assessed. The mammary epithelial tree of the high-birth-weight offspring was denser, contained more terminal end buds and exhibited higher number of proliferating cells. Further, their mammary glands expressed lower levels of ER-alpha, but higher levels of activated MAPK. No alterations in apoptosis were noted. High-birth-weight rats developed 7,12-dimethylbenz[a]anthracene-induced mammary tumors significantly earlier, and tumors grew larger than in the controls. The tumors in this group expressed higher levels of leptin receptor and activated Akt, and contained fewer apoptotic cells than those in the controls. Our results indicate that high birth weight is related to shortened latency to develop mammary tumors-perhaps reflecting an increase in activated MAPK levels and increased tumor growth-perhaps caused by a lower apoptotic response due to higher leptin receptor and activated Akt levels in the tumors. (c) 2006 Wiley-Liss, Inc.