Cell-type specific regulation of human interstitial collagenase-1 gene expression by interleukin-1 beta (IL-1 beta) in human fibroblasts and BC-8701 breast cancer cells
Cell-type specific regulation of human interstitial collagenase-1 gene expression by interleukin-1 beta (IL-1 beta) in human fibroblasts and BC-8701 breast cancer cells
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DOI：
10.1002/(sici)1097-4644(19970901)66:3
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发表时间：
1997-09-01
影响因子：
4
通讯作者：
Brinckerhoff, CE
中科院分区：
文献类型：
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作者：
Rutter, JL;Benbow, U;Brinckerhoff, CE
白细胞介素-1 β（IL-1 β）是一种有效的细胞因子，可刺激间质胶原酶-1（基质金属蛋白酶-1; MMP-1）。在这项研究中，我们比较了IL-1 β在两种非常不同的细胞中诱导胶原酶基因表达的机制，这两种细胞是正常人包皮成纤维细胞（HFF）和侵袭性乳腺癌细胞系BC-8701细胞;北方分析表明，胶原酶诱导的时间过程在两种细胞中是不同的：虽然两种细胞都表达低水平的MMP-1，但IL-1 β的加入在1小时时增加了HFF中的MMP-1 mRNA，并且在24小时内水平保持较高。相反，IL-1 β处理的BC-8701细胞中MMP-1水平直到4 h才升高，72 h达到峰值，然后下降。为了分析转录应答，我们克隆并测序了超过4，300 bp的人MMP-1启动子，并从该启动子克隆制备了一系列与荧光素酶报告基因连接的5 '缺失构建体，并将这些构建体瞬时转染到两种细胞类型中以测量基础和IL-1 β诱导的转录。当两种细胞类型未被诱导时，含有小于2，900 bp的启动子片段仅产生最小的转录应答，而较大的片段显示出增加的转录活性。用IL-1 β处理，HFF中仅观察到较大片段的显著反应性（P < 0.001），而在BC-8701细胞中，所有片段均被IL-1 β显著诱导。最后，我们发现IL-1 β稳定正常成纤维细胞中的MMP-1 mRNA，但在BC-8701乳腺癌细胞中不稳定。我们的结论是，MMP-1基因表达的转录和转录后调控IL-1 β是由细胞类型的特异性机制，我们认为，IL-1诱导MMP-1在肿瘤细胞和邻近的基质细胞表达可能会放大肿瘤细胞的侵袭能力。(C)1997 Wiley利斯公司
Interleukin-1 beta (IL-1 beta) is a potent cytokine that stimulates interstitial collagenase-1 (matrix metalloproteinase-1; MMP-1). in this study, eve compared the mechanism(s) by which IL-1 beta induces collagenase gene expression in two very different cells, normal human foreskin fibroblasts (HFFs) and an aggressive breast cancer cell line, BC-8701 cells; Northern analysis showed that the time course of collagenase induction was distinct in the two cells: although both cells expressed low levels of MMP-1 constitutively addition of IL-1 beta increased MMP-1 mRNA in HFFs by 1 h and levels remained high over a 24-h period. In contrast, MMP-1 levels in IL-1 beta-treated BC-8701 cells did not increase until 4 h, peaked by 72 h and then declined. To analyze the transcriptional response, we cloned and sequenced more than 4,300 bp of the human MMP-1 promoter, and from this promoter clone, we prepared a series of 5'-deletion constructs linked to the luciferase reporter and transiently transfected these constructs into both cell types to measure both basal and IL-1 beta induced transcription. When both cell types were uninduced, promoter fragments containing less than 2,900 bp gave only a minimal transcriptional response, while larger fragments showed increased transcriptional activity. With IL-1 beta treatment, significant responsiveness (P < 0.001) in HFFs was seen only with the larger fragments, while in the BC-8701 cells, all fragments were significantly induced with IL-1 beta. Finally, we found that IL-1 beta stabilized MMP-1 mRNA in normal fibroblasts, but not in BC-8701 breast cancer cells. We conclude that both the transcriptional and post-transcriptional regulation of MMP-1 gene expression by IL-1 beta is controlled by cell-type specific mechanisms, and we suggest that IL-1 induced MMP-1 expression in tumor cells and in neighboring stroma[ cells may amplify the invasive ability of tumor cells. (C) 1997 Wiley Liss, Inc.