Loss of protein kinase C delta alters mammary gland development and apoptosis.
Loss of protein kinase C delta alters mammary gland development and apoptosis.
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DOI：
10.1038/cddis.2009.20
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发表时间：
2010
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
由于凋亡途径通常在乳腺癌中失调，因此探索乳腺细胞死亡是如何调节的对于理解人类疾病至关重要。我们发现，蛋白激酶C δ（PKCδ）−/−小鼠的原代乳腺上皮细胞对体外凋亡剂的反应受到抑制。在体内乳腺中，细胞凋亡对于青春期乳腺导管形态发生和泌乳后的退化至关重要。我们在这两个关键窗口期间探索了PKCδ −/−小鼠的乳腺发育。在4- 6周龄的PKCδ −/−小鼠中，分支形态发生发生改变，如导管分支减少所示;然而，末端芽中的凋亡和增殖没有改变。相反，在PKCδ −/−小鼠中，退化过程中caspase-3的激活被延迟，但退化正常进行。胸腺也会对生理信号作出反应而发生细胞凋亡。在用辐射处理的PKCδ −/−小鼠的胸腺中观察到半胱天冬酶-3活化的显著抑制，但用地塞米松处理的小鼠没有，这表明在体内细胞凋亡途径的执行中存在靶向和组织依赖性差异。这些发现强调了PKCδ在乳腺细胞凋亡和非凋亡过程中的作用，并强调了体内凋亡途径的冗余。
As apoptotic pathways are commonly deregulated in breast cancer, exploring how mammary gland cell death is regulated is critical for understanding human disease. We show that primary mammary epithelial cells from protein kinase C delta (PKCδ) −/− mice have a suppressed response to apoptotic agents in vitro. In the mammary gland in vivo, apoptosis is critical for ductal morphogenesis during puberty and involution following lactation. We have explored mammary gland development in the PKCδ −/− mouse during these two critical windows. Branching morphogenesis was altered in 4- to 6-week-old PKCδ −/− mice as indicated by reduced ductal branching; however, apoptosis and proliferation in the terminal end buds was unaltered. Conversely, activation of caspase-3 during involution was delayed in PKCδ −/− mice, but involution proceeded normally. The thymus also undergoes apoptosis in response to physiological signals. A dramatic suppression of caspase-3 activation was observed in the thymus of PKCδ −/− mice treated with irradiation, but not mice treated with dexamethasone, suggesting that there are both target- and tissue-dependent differences in the execution of apoptotic pathways in vivo. These findings highlight a role for PKCδ in both apoptotic and nonapoptotic processes in the mammary gland and underscore the redundancy of apoptotic pathways in vivo.
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线粒体结构和功能的改变是地塞米松诱导的胸腺细胞凋亡的早期事件。
影响因子：
7.8
作者：
Petit, P X;Lecoeur, H;Zorn, E;Dauguet, C;Mignotte, B;Gougeon, M L
通讯作者：
Gougeon, M L
影响因子：
11.8
作者：
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通讯作者：
Brugge, Joan S.
影响因子：
2.5
作者：
Richert, MM;Schwertfeger, KL;Anderson, SM
通讯作者：
Anderson, SM
影响因子：
3.3
作者：
Reno, Elaine M.;Haughian, James M.;Bradford, Andrew P.
通讯作者：
Bradford, Andrew P.
影响因子：
8
作者：
D'Costa, AM;Robinson, JK;Denning, MF
通讯作者：
Denning, MF