EXPRESSION OF STROMELYSIN-1 AND TIMP-1 IN THE INVOLUTING MAMMARY-GLAND AND IN EARLY INVASIVE TUMORS OF THE MOUSE
EXPRESSION OF STROMELYSIN-1 AND TIMP-1 IN THE INVOLUTING MAMMARY-GLAND AND IN EARLY INVASIVE TUMORS OF THE MOUSE
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DOI：
10.1002/ijc.2910590421
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发表时间：
1994-11-15
影响因子：
6.4
通讯作者：
ANDRES, AC
中科院分区：
文献类型：
--
作者：
LI, F;STRANGE, R;ANDRES, AC
乳腺在哺乳后复旧期间经历广泛的组织重建。这一过程是由细胞外基质降解酶及其抑制剂的协同表达所控制的。在癌变过程中，肿瘤细胞的侵袭性生长以基底膜穿透和间质侵袭为特征。我们比较了组织重塑酶基质金属蛋白酶-1及其抑制剂基质金属蛋白酶组织抑制剂-1（TIMP-1）在小鼠乳腺退化和癌变过程中的表达。在退化的乳腺中，基质分解素-1在肌上皮细胞中表达，而TIMP-1仅限于间质组织。为了分析这些组织重塑基因在肿瘤发展中的参与，我们研究了在乳蛋白基因启动子控制下表达激活的Ha-ras或c-myc癌基因的转基因小鼠的乳腺肿瘤。在未分化和转移Ha-res诱导的肿瘤中，基质溶解素-1的表达与退化中的表达相当，而TIMP-1的表达大大升高。在Ha-ras诱导的癌变过程中，首先在癌前病变周围的肌上皮细胞中检测到基质溶解素-1表达。相反，在由c-myc诱导的高分化和非转移性乳腺肿瘤中，没有观察到任何基因的表达。因此，基质分解素-1和TIMP-1的表达仅限于侵袭性生长的肿瘤，并且在癌发生的最早阶段被诱导。(C)1994 Wiley-Liss，Inc.
The mammary gland, during post-lactational involution, is subjected to extensive tissue reconstruction. This process is governed by the concerted expression of extracellular-matrix-degrading enzymes and their inhibitors. During carcinogenesis, the invasive growth of tumor cells is characterized by the penetration of the basement membrane and stromal invasion. We compared the expression of the tissue-remodeling enzymes stromelysin-1, a matrix metalloproteinase, and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), during mammary gland involution and carcinogenesis in mouse. In involuting mammary glands, stromelysin-1 was expressed in myoepithelial cells, whereas TIMP-1 was confined to the stromal tissue. To analyze the involvement of these tissue-remodeling genes in tumor development, we examined mammary tumors of transgenic mice expressing either the activated Ha-ras or c-myc oncogene under the control of a milk-protein gene promoter. In the undifferentiated and metastasizing Ha-res-induced tumors, stromelysin-1 expression was comparable to that seen in involution, whereas TIMP-1 expression was greatly elevated. During Ha-ras-induced carcinogenesis, stromelysin-1 expression was first detected in the myo-epithelial cells surrounding preneoplastic lesions. In contrast, in the well-differentiated and non-metastatic mammary tumors induced by c-myc, no expression of either gene was observed. Thus, expression of stromelysin-1 and TIMP-1 is confined to the aggressively growing tumors and is induced in the earliest stages of carcinogenesis. (C) 1994 Wiley-Liss, Inc.