Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution
Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution
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DOI：
10.1073/pnas.94.7.3425
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Furth, PA
中科院分区：
文献类型：
--
作者：
Li, ML;Liu, XW;Furth, PA
在退化过程中，乳腺肺泡细胞的程序性细胞死亡（PCD）在哺乳结束后数小时内开始，局部，乳汁在肺泡腔内积聚;全身，催乳激素水平下降，四个实验模型被用来定义局部因素的作用，与第一和第二阶段的退化过程中的全身激素相比。在三种模型中，在存在全身性催乳激素的情况下，乳汁释放被破坏：（i）乳头的封闭，（ii）由于缺乏乳头连接而不能释放乳汁的乳腺移植，和（iii）催产素基因的失活。使用第四种泌乳失败的转基因模型说明了全身激素保持小叶-肺泡结构而不阻断PCD的能力，在退化的第一阶段，即使在全身性催乳激素存在的情况下，局部信号也足以诱导肺泡PCD，PCD与bas诱导、乳蛋白表达减少、通过Stat 5a和5 b的催乳素信号转导阻断以及Stall的激活一致，乳腺退化的两个阶段是由死亡信号的逐渐增加和存活因子的丧失所调节的，这项研究表明，在第一个可逆阶段发生的遗传事件是由局部因素控制的，这些乳腺来源的死亡信号是占主导地位的保护作用与全身激素刺激。
Programmed cell death (PCD) of mammary alveolar cells during involution commences within hours of the end of suckling, Locally, milk accumulates within alveolar lumens; systemically, levels of lactogenic hormones fall, Four experimental models were used to define the role of local factors as compared with systemic hormones during the first and second stages of involution. In three models, milk release was disrupted in the presence of systemic lactogenic hormones: (i) sealing of the teats, (ii) mammary gland transplants that cannot release milk due to the absence of a teat connection, and (iii) inactivation of the oxytocin gene, The ability of systemic hormones to preserve lobular-alveolar structure without blocking PCD was illustrated using a fourth transgenic model of lactation failure, During the first stage of involution, local signals were sufficient to induce alveolar PCD even in the presence of systemic lactogenic hormones, PCD coincided with bas induction, decreased expression of milk proteins, block of prolactin signal transduction through Stat5a and 5b, and activation of Stall, The two stages of mammary gland involution are regulated by progressive gain of death signals and loss of survival factors, This study demonstrates that genetic events that occur during the first reversible stage are controlled by local factors, These mammary-derived death signals are dominant over protective effects related to systemic hormone stimulation.