Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-b receptor exhibit impaired mammary development and enhanced mammary tumor formation
Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-b receptor exhibit impaired mammary development and enhanced mammary tumor formation
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DOI：
10.1016/s0002-9440(10)63510-9
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发表时间：
2003-10-01
影响因子：
6
通讯作者：
Moses, HL
中科院分区：
文献类型：
--
作者：
Gorska, AE;Jensen, RA;Moses, HL
我们之前的研究表明，在MMTV启动子/增强子的控制下，乳腺上皮中显性阴性的II型转化生长因子- β受体（DNIIR）的表达会导致处女小鼠的肺泡增生和分化。在这里，我们发现MMTV-DNIIR雌性小鼠在妊娠早期加速了乳腺分化，在妊娠晚期和哺乳期发育受损，随后延迟了哺乳期后的复归。乳腺肿瘤，主要是原位癌，在MMTV-DNIIR小鼠中自发发展，中位潜伏期长（27.5个月）。与mmtv -转化生长因子(TGF)- α小鼠杂交获得表达两种转基因的小鼠，其乳腺肿瘤形成潜伏期比仅表达mmtv -TGF- α转基因的小鼠更短(
We have previously shown that expression of a dominant-negative type II transforming growth factor-beta receptor (DNIIR) in mammary epithelium under control of the MMTV promoter/enhancer causes alveolar hyperplasia and differentiation in virgin mice. Here we show that MMTV-DNIIR female mice have accelerated mammary gland differentiation during early pregnancy with impaired development during late pregnancy and lactation followed by delayed postlactational involution. Mammary tumors, mostly carcinoma in situ, developed spontaneously in the MMTV-DNIIR mice with a long median latency (27.5 months). Crossbreeding to MMTV-transforming growth factor (TGF)-alpha mice to obtain mice expressing both transgenes resulted in mammary tumor formation with a much shorter latency more similar to those expressing only the MMTV-TGF-alpha transgene (