Pregnancy and stem cell behavior
Pregnancy and stem cell behavior
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DOI：
10.1007/s10911-005-2538-1
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发表时间：
2005-01-01
影响因子：
2.5
通讯作者：
Smith, GH
中科院分区：
文献类型：
--
作者：
Wagner, KU;Smith, GH
癌症起始上皮亚型（即癌症干细胞）的鉴定对于更全面地了解肿瘤转化和肿瘤发生的过程非常重要。由于生殖史对乳腺肿瘤发生有重要影响，因此可以合理地假设妊娠和哺乳对多能祖细胞的癌症易感性具有持久影响。使用Cre-lox技术作为遗传标记妊娠激素反应细胞的工具，我们确定了一种在经产女性中丰富的乳腺上皮亚型。这些妊娠诱导的乳腺上皮细胞（PI-MEC）起源于第一次妊娠和哺乳周期期间的分化细胞。它们在哺乳后重构期间不发生细胞凋亡，并且在女性生命的剩余时间内持续存在。在这篇综述中，我们讨论了PI-MEC的生物学相关性在经产女性和他们的重要干细胞样功能，如自我更新，以及他们的能力，以产生后代不同的细胞命运。使用适当的动物模型，我们进一步证明PI-MEC是妊娠增强乳腺肿瘤发生的细胞靶点。
The identification of cancer-initiating epithelial subtypes (i.e. cancer stem cells) is important for gaining a more comprehensive understanding of the process of neoplastic transformation and tumorigenesis. Since reproductive history has a major impact on breast tumorigenesis, it is reasonable to assume that pregnancy and lactation have enduring effects on the cancer susceptibility of multipotent progenitors. Using the Cre-lox technology as a tool to genetically label pregnancy-hormone-responsive cells, we identified a mammary epithelial subtype that is abundant in parous females. These pregnancy-induced mammary epithelial cells (PI-MECs) originate from differentiating cells during the first pregnancy and lactation cycle. They do not undergo apoptosis during postlactational remodeling, and they persist throughout the remainder of a females life. In this review, we discuss the biological relevance of PI-MECs in multiparous females and their important stem cell-like features, such as self renewal, as well as their ability to produce progeny with diverse cellular fates. Using appropriate animal models, we further demonstrate that PI-MECs are cellular targets for pregnancy-enhanced mammary tumorigenesis.