v‐src activation of the collagenase‐1 (matrix metalloproteinase‐1) promoter through PEA3 and STAT: Requirement of extracellular signal‐regulated kinases and inhibition by retinoic acid receptors
v‐src activation of the collagenase‐1 (matrix metalloproteinase‐1) promoter through PEA3 and STAT: Requirement of extracellular signal‐regulated kinases and inhibition by retinoic acid receptors
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DOI：
10.1002/(sici)1098-2744(199803)21:3
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发表时间：
1998-03
影响因子：
4.6
通讯作者：
M. Vincenti;D. Schroen;C. I. Coon;C. Brinckerhoff
中科院分区：
文献类型：
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作者：
M. Vincenti;D. Schroen;C. I. Coon;C. Brinckerhoff
胶原酶-1（基质金属蛋白酶-1（MMP-1））降解细胞外基质并增强肿瘤细胞的侵袭表型。 v-src通过近端启动子中的一系列元件激活MMP-1转录，包括E2BP（nt-172）、多瘤病毒增强子A3（PEA3）（nt-94）、激活蛋白-1（AP-1）（nt-72）以及信号转导子和转录激活子（STAT）（nt-57）共有位点。在这些位点中，PEA3 和 STAT 特别有助于 v-src 的诱导，而其余元件也参与佛波酯佛波醇肉豆蔻酸酯乙酸酯 (PMA) 的诱导。然而，与 PMA 诱导 MMP-1 相比，位于 nt-186 的 AP-1 位点对 v-src 诱导没有贡献。这些结果表明酪氨酸激酶和蛋白激酶 C 依赖性途径在 MMP-1 转录方面存在差异。 v-src 通过丝裂原激活蛋白激酶诱导 MMP-1，细胞外信号调节激酶比 c-jun N 末端激酶发挥更大的作用。视黄酸可抑制某些癌症的进展，并抑制 v-src 诱导的 MMP-1 转录。视黄酸受体 (RAR) α 或 β（而非 γ）或类视黄醇 X 受体 α 的组成型表达抑制 v-src 诱导的胶原酶-1 转录。我们得出的结论是，v-src 对 MMP-1 的致癌诱导取决于信号通路和顺式作用序列，这些信号通路和顺式作用序列与参与佛波酯激活的序列不同。此外，MMP-1 的 v-src 诱导可能通过与其他基因协同作用，增强基质降解和肿瘤进展，而视黄酸和 RAR 可能以 RAR 类型特异性方式拮抗这种诱导。摩尔。致癌。 21:194–204, 1998。© 1998 Wiley-Liss, Inc.
Collagenase‐1 (matrix metalloproteinase‐1 (MMP‐1)) degrades the extracellular matrix and enhances the invasive phenotype of tumor cells. v‐src activated MMP‐1 transcription through a series of elements in the proximal promoter, including the E2BP (nt‐172), polyoma virus enhancer A3 (PEA3) (nt‐94), activator protein‐1 (AP‐1) (nt‐72), and signal transducer and activator of transcription (STAT) (nt‐57) consensus sites. Of these sites, PEA3 and STAT contributed specifically to induction by v‐src, whereas the remaining elements were also involved in induction by the phorbol ester phorbol myristate acetate (PMA). However, in contrast to MMP‐1 induction by PMA, an AP‐1 site located at nt‐186 did not contribute to v‐src induction. These results suggest divergence of the tyrosine kinase– and protein kinase C–dependent pathways with respect to MMP‐1 transcription. v‐src induced MMP‐1 through mitogen‐activated protein kinases, with extracellular signal–regulated kinases playing a larger role than c‐jun N‐terminal kinase. Retinoic acid, which inhibits the progression of certain cancers, repressed v‐src–induced MMP‐1 transcription. Constitutive expression of retinoic acid receptors (RARs) α or β, but not γ, or of retinoid X receptor α, repressed v‐src–induced collagenase‐1 transcription. We concluded that oncogenic induction of MMP‐1 by v‐src depends on signaling pathways and cis‐acting sequences that are distinct from those involved in phorbol ester activation. Furthermore, v‐src induction of MMP‐1 may, by acting in concert with other genes, enhance matrix degradation and tumor progression, and retinoic acid and RARs may antagonize this induction in an RAR type–specific manner. Mol. Carcinog. 21:194–204, 1998. © 1998 Wiley‐Liss, Inc.