流体蛋白酶MMP3/stromelysin-1促进乳腺癌的发生
M D Sternlicht1, A Lochter, C J Sympson
1Department of Anatomy, University of California, San Francisco 94143-0452, USA. sternli@itsa.ucsf.edu
Cell
|July 31, 1999
概括
矩阵金属蛋白酶3 (MMP3 / Str1) 驱动乳腺瘤的启动和入侵. 一旦形成,瘤变得独立于MMP3 / Str1,突出显示其在瘤风险中的作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 矩阵金属蛋白酶 (MMPs) 在癌细胞层上升调节,促进侵袭和转移.
- MMP3,也称为 stromelysin-1 (Str1),与上皮癌的进展有关.
研究的目的:
- 研究MMP3/Str1在乳腺瘤发病,侵袭和瘤风险中的作用.
- 为了确定Str1的表达是否会影响前恶性和恶性病变的发展.
主要方法:
- 在体内在表型正常的乳腺上皮细胞中利用四环素调节的MMP3/Str1表达.
- 产生了具有乳腺特异性Str1表达的转基因小鼠.
- 评估瘤形成,侵入性和基因组变化.
- 研究了TIMP1共同表达对Str1诱导变化的影响.
主要成果:
- MMP3/Str1表达诱导了来自正常乳腺上皮细胞的侵袭性中瘤类瘤.
- 瘤在启动后变得独立于持续的Str1表达.
- 在小鼠乳腺中,Str1促进了自发的前恶性变化和恶性转化.
- 同时表达TIMP1阻断了Str1诱导的前恶性和恶性病变.
- 与其他小鼠模型相比,病变表现出独特的基因组变化.
结论:
- MMP3/Str1在启动乳腺瘤和改变瘤风险方面发挥着关键作用.
- Str1 影响瘤开始和进展,独立于持续表达.
- TIMP1 作为Str1介导瘤发生的抑制剂.
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