Berryhill Grace E, Lemay Danielle G, Trott Josephine F, Aimo Lucila, Lock Adam L, Hovey Russell C
Department of Animal Science, University of California Davis, Davis, California 95616-8521.
UC Davis Genome Center, University of California Davis, Davis, California 95616-8521.
Endocrinology. 2017 Oct 1;158(10):3126-3139. doi: 10.1210/en.2017-00395.
Allometric growth of ducts in the mammary glands (MGs) is widely held to be estrogen dependent. We previously discovered that the dietary fatty acid trans-10, cis-12 conjugated linoleic acid (CLA) stimulates estrogen-independent allometric growth and terminal end bud formation in ovariectomized mice. Given the similar phenotype induced by estrogen and CLA, we investigated the shared and/or divergent mechanisms underlying these changes. We confirmed MG growth induced by CLA is temporally distinct from that elicited by estrogen. We then used RNA sequencing to compare the transcriptome of the MG during similar proliferative and morphological states. Both estrogen and CLA affected the genes involved in proliferation. The transcriptome for estrogen-treated mice included canonical estrogen-induced genes, including Pgr, Areg, and Foxa1. In contrast, their expression was unchanged by CLA. However, CLA, but not estrogen, altered expression of a unique set of inflammation-associated genes, consistent with stromal changes. This CLA-altered signature included increased expression of epidermal growth factor receptor (EGFR) pathway components, consistent with the demonstration that CLA-induced MG growth is EGFR dependent. Our findings highlight a unique role for diet-induced inflammation that underlies estrogen-independent MG development.
乳腺（MG）中导管的异速生长普遍被认为是雌激素依赖性的。我们先前发现，膳食脂肪酸反式-10，顺式-12共轭亚油酸（CLA）可刺激去卵巢小鼠体内雌激素非依赖性的异速生长和终末芽形成。鉴于雌激素和CLA诱导的表型相似，我们研究了这些变化背后的共同和/或不同机制。我们证实，CLA诱导的MG生长在时间上与雌激素引起的不同。然后，我们使用RNA测序来比较处于相似增殖和形态状态下MG的转录组。雌激素和CLA均影响参与增殖的基因。雌激素处理小鼠的转录组包括典型的雌激素诱导基因，如Pgr、Areg和Foxa1。相比之下，它们的表达不受CLA影响。然而，CLA而非雌激素改变了一组独特的炎症相关基因的表达，这与基质变化一致。这种CLA改变的特征包括表皮生长因子受体（EGFR）途径成分的表达增加，这与CLA诱导的MG生长是EGFR依赖性的证明一致。我们的研究结果突出了饮食诱导的炎症在雌激素非依赖性MG发育中的独特作用。
