Zhang M, Maass N, Magit D, Sager R
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Cell Growth Differ. 1997 Feb;8(2):179-86.
Tumor invasion and metastasis are processes poorly understood at the molecular level. Maspin is a serine protease inhibitor (serpin) with tumor-suppressing function in the mammary gland. Maspin gene expression is decreased with malignancy and is lost in metastatic cells. We show in this report that differential expression of maspin in normal and carcinoma-derived mammary epithelial cells is regulated at the transcriptional level. We have identified the Ets and Ap1 sites in the maspin promoter that are active in regulating maspin expression in normal mammary epithelial cells but inactive in tumor cells. The Ets site alone is sufficient to activate transcription in a heterologous promoter, whereas the Ap1 site cooperates with Ets in activation. The enhancing function by Ets and Ap1 elements is decreased in primary tumor cells (21NT) and is abolished in invasive tumor cells (MDA-231). Thus, loss of maspin expression during tumor progression results at least in part from the absence of transactivation through the Ets and Ap1 sites.
肿瘤侵袭和转移是在分子水平上了解甚少的过程。Maspin是一种丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂），在乳腺中具有肿瘤抑制功能。Maspin基因表达随恶性程度降低，在转移细胞中丢失。我们在本报告中表明，maspin在正常和癌源乳腺上皮细胞中的差异表达在转录水平上受到调控。我们已经确定了maspin启动子中的Ets和Ap1位点，它们在正常乳腺上皮细胞中激活maspin表达，但在肿瘤细胞中无活性。单独的Ets位点足以在异源启动子中激活转录，而Ap1位点与Ets协同激活。Ets和Ap1元件的增强功能在原发性肿瘤细胞（21NT）中降低，在侵袭性肿瘤细胞（MDA-231）中消失。因此，肿瘤进展过程中maspin表达的丧失至少部分是由于缺乏通过Ets和Ap1位点的反式激活。
