...
首页> 外文期刊>Oncogene >Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-|[beta]|1 expression
【24h】

Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-|[beta]|1 expression

机译:奇偶性诱导的小鼠乳腺上皮细胞是多能的,自我更新的并且对TGF- |β| 1表达敏感

获取原文
           

摘要

A parity-induced mammary population, marked by -galactosidase expression conditionally activated through cre-lox recombinase originates in WAP-Cre/Rosa-lox-STOP-lox-LacZ (WAP-Cre/Rosa-LacZ) female mice during pregnancy, lactation and involution. During subsequent pregnancies, these parity-induced mammary epithelial cells (PI-MEC) proliferated to produce new secretory acini composed of secretory luminal cells and myoepithelium. In serial transplantation assays, PI-MEC were able to self-renew over several transplant generations and to contribute significantly to the resulting mammary outgrowths. In limiting dilution transplantation, they proliferated to produce both luminal and myoepithelial cells, comprised both lobule-limited and duct-limited epithelial outgrowths, and differentiated into all the cellular subtypes recognized in murine mammary epithelium. TGF-1 expression from the whey acidic protein promoter (WAP) in triply transgenic females did not prevent the appearance of PI-MEC after pregnancy despite the absence of full lactation or their ability to proliferate and produce progeny with diverse cellular fates in situ upon subsequent pregnancies. However, in transplants from triple transgenic parous females, the WAP-TGF-1-positive PI-MEC did not contribute to the newly recapitulated mammary outgrowths, suggesting that they were incapable of expansive cellular proliferation (self-renewal). This result is consistent with our earlier publication that WAP-TGF-1 expression in mammary epithelium induces premature stem cell senescence in mammary transplants and decreases mammary cancer risk in mouse mammary tumor virus (MMTV)-infected females even after multiple pregnancies.
机译:通过cre-lox重组酶有条件激活的以-半乳糖苷酶表达为标志的奇偶性诱导的哺乳动物种群起源于妊娠,哺乳和内卷化。在随后的怀孕期间,这些奇偶性诱导的乳腺上皮细胞(PI-MEC)增殖产生新的分泌性腺泡,该分泌性腺泡由分泌性腔内细胞和肌上皮组成。在系列移植试验中,PI-MEC能够在几代移植中自我更新,并为导致的乳腺增生做出了重要贡献。在有限稀释移植中,它们增殖以产生管腔和肌上皮细胞,既包含小叶受限的上皮细胞生长,也包含导管受限的上皮生长,并分化为鼠乳腺上皮中识别的所有细胞亚型。尽管缺乏充分的泌乳或它们的增殖能力和产生子代的能力,但三联转基因女性在乳腺酸性蛋白启动子(WAP)中的TGF-1表达并不能阻止PI-MEC的出现,并在随后的生命中产生多种细胞命运怀孕。但是,在来自三重转基因双亲雌性的移植物中,WAP-TGF-1阳性的PI-MEC不会促进新近再现的乳腺增生,这表明它们无法进行广泛的细胞增殖(自我更新)。该结果与我们先前的出版物一致,即在乳腺上皮中的WAP-TGF-1表达在乳腺移植中诱导干细胞衰老,即使在多次怀孕后,受小鼠乳腺肿瘤病毒(MMTV)感染的女性也降低了患乳腺癌的风险。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号