Sympson C J, Bissell M J, Werb Z
Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720, USA.
Semin Cancer Biol. 1995 Jun;6(3):159-63. doi: 10.1006/scbi.1995.0022.
An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.
完整的基底膜（BM）对于许多上皮细胞的正常功能、分化和形态至关重要。在正常发育以及疾病状态下，都会发生这种基底膜的破坏或缺失。为了研究基底膜在体内乳腺发育过程中的重要性，我们构建了转基因小鼠，这些小鼠会不适当表达基质金属蛋白酶基质溶素-1的自激活异构体。这些小鼠的乳腺在整个发育过程中，其功能和形态都发生了改变。我们现已记录到这些小鼠的几个独立品系中乳腺癌的发病率极高。这些数据表明，基质溶素-1的过表达和基底膜的破坏可能是乳腺癌多步骤进程中的关键一步。
