Rochefort H
Unité Hormones et Cancer (U 148) INSERM, University of Montpellier, France.
Breast Cancer Res Treat. 1990 Jul;16(1):3-13. doi: 10.1007/BF01806570.
Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans and to activate other proteinases in acidic microenvironments. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in lymph node-negative tumors. These results suggest that overexpression and possible derouting of cathepsin D plays an important role in invasion and metastasis of breast cancer.
组织蛋白酶D是一种存在于所有细胞中的酸性溶酶体蛋白酶。在雌激素受体阳性和阴性的乳腺癌细胞系中，编码组织蛋白酶D原的mRNA过度表达，且该酶原的分选和成熟过程发生改变，导致活性蛋白酶在大的内体中积累，并分泌前体（52K蛋白）。在MCF7细胞中，组织蛋白酶D mRNA由雌激素直接转录诱导，并由生长因子间接诱导。在体外，组织蛋白酶D原是乳腺癌细胞上的一种自分泌有丝分裂原，在酸性微环境中可被自身激活，以降解细胞外基质和蛋白聚糖，并激活其他蛋白酶。在患者中，原发性乳腺癌细胞溶质中高浓度的组织蛋白酶D与转移的发生显著相关。该标志物独立于其他预后因素，在淋巴结阴性肿瘤中似乎特别有用。这些结果表明，组织蛋白酶D的过度表达和可能的异常转运在乳腺癌的侵袭和转移中起重要作用。
