Transcriptional regulation of vascular endothelial growth factor expression in epithelial and stromal cells during mouse mammary gland development
Transcriptional regulation of vascular endothelial growth factor expression in epithelial and stromal cells during mouse mammary gland development
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DOI：
10.1210/me.15.5.819
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发表时间：
2001-05-01
影响因子：
--
通讯作者：
Vonderhaar, BK
中科院分区：
文献类型：
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作者：
Hovey, RC;Goldhar, AS;Vonderhaar, BK
伴随着乳腺发育和功能的变化，是一个对乳汁生成和肿瘤形成至关重要的血管网络的建立。血管内皮生长因子(VEGF)是调节血管发育的一种重要的血管生成和通透性因子，与上皮-间质的相互作用有关。RT-PCR对血管内皮生长因子转录的分析表明，未分娩女性乳腺中均有三种不同亚型(VEGF(120)、(164)、(188))的mRNA表达。在妊娠期间，随着血管内皮生长因子(120)和血管内皮生长因子(164)mRNAs丰度的增加，血管内皮生长因子(188)水平下降，在哺乳期间检测不到，在整个发育过程中，这三种异构体在清除的乳脂垫中表达水平一致。此外，不同时期大网膜脂肪组织中VEGF(188)mRNA的存在证实了VEGF(188)在乳腺内脂肪组织中特异表达。利用3T3-L1前脂肪细胞证实，VEGF(188)mRNA转录是脂肪形成过程中的晚期事件，不同于分化过程中早期诱导的VEGF(120)和VEGF(164)mRNA的诱导。而HC11乳腺上皮细胞仅表达VEGF(120)和VEGF(164)。血管内皮细胞生长因子基因和蛋白的定位显示，初产女性乳腺间质细胞中有血管内皮生长因子的表达，并在哺乳期经历向上皮细胞表达的转变。相比之下，VEGF受体Flk-1和Flt-1的mRNA在处女期和妊娠期定位于乳房脂肪垫内的间质细胞，并在哺乳期表达于以上皮细胞为基础的间质组织。综上所述，这些结果支持这样的结论，即血管内皮生长因子是由乳腺内特定类型的细胞差异转录的，在激素调节下，它以自分泌/旁分泌的方式发挥作用。
Accompanying changes in the development and function of the mammary gland is the establishment of a vascular network of critical importance for lactogenesis and tumorigenesis. A potent angiogenic and permeability factor that regulates vascular development in association with epithelial-stromal interactions is vascular endothelial growth factor (VEGF), Analysis of VEGF transcription by RT-PCR revealed mRNA for all three VEGF isoforms (VEGF(120), (164), (188)) within the mammary gland of nulliparous females. During pregnancy the level of VEGF(188) declined and became undetectable during lactation in association with the increased abundance of VEGF(120) and VEGF(164) mRNAs, All three isoforms were expressed at consistent levels within the cleared mammary fat pad throughout development. Furthermore, the presence of VEGF(188) mRNA in omental adipose tissue at various stages established that VEGF(188) is expressed specifically in adipose tissue within the mammary gland, Using 3T3-L1 preadipocytes it was demonstrated that VEGF(188) mRNA transcription occurs as a late event during lipogenesis distinct from earlier induction of VEGF(120) and VEGF(164) mRNA during differentiation. In contrast, HC11 mammary epithelial cells only expressed mRNA for VEGF(120) and VEGF(164). Localization of VEGF mRNA and protein revealed that VEGF is expressed in stromal cells of the mammary gland in nulliparous females and then undergoes a transition to epithelial expression during lactation. By contrast, mRNA for the VEGF receptors, Flk-1 and Flt-1, localized to stromal cells within the mammary fat pad during virgin and gestational development and was expressed in the interstitial tissue basal to epithelial cells during lactation. Taken together, these results support the conclusion that VEGF is differentially transcribed by specific cell types within the mammary gland, and that under hormonal regulation it functions in an autocrine/paracrine manner.