The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors
The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors
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DOI：
10.1038/sj.onc.1208733
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发表时间：
2005-09-01
期刊：
影响因子：
8
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Echizenya, M;Kondo, S;Noda, M
膜锚定的MMP调节因子RECK在许多实体瘤中下调; RECK下调的程度与不良预后相关。RECK在肿瘤细胞中的强制表达导致血管生成、侵袭和转移的抑制。因此，对RECK基因在正常发育过程中的作用和调节机制的研究可能会对肿瘤细胞的恶性行为如何产生以及如何控制产生重要的见解。我们以前的研究表明，缺乏RECK的小鼠在E10.5左右死亡，组织完整性降低。在本研究中，我们发现，在后期野生型胚胎，RECK是丰富的表达在骨骼肌，特别是在成肌细胞分化因子MRF 4的表达区域。与这一发现一致，RECK启动子在培养的细胞中被MRF 4激活。相反，成肌细胞决定因子MyoD抑制RECK启动子。缺乏RECK表达的成肌细胞比表达RECK的细胞以更高的效率产生肌管，表明RECK抑制肌管形成。这些发现表明，MyoD下调RECK以促进肌管形成，而MRF 4上调RECK以促进需要细胞外基质完整性的肌生成的其他方面。
The membrane-anchored MMP-regulator RECK is down regulated in many solid tumors; the extent of RECK down regulation correlates with poor prognosis. Forced expression of RECK in tumor cells results in suppression of angiogenesis, invasion, and metastasis. Studies on the roles and the mechanisms of regulation of the RECK gene during normal development may therefore yield important insights into how the malignant behaviors of tumor cells arise and how they can be controlled. Our previous studies indicate that mice lacking RECK die around E10.5 with reduced tissue integrity. In the present study, we have found that in later stage wild-type embryos, RECK is abundantly expressed in skeletal muscles, especially in the areas where the myoblast differentiation factor MRF4 is expressed. Consistent with this finding, the RECK-promoter is activated by MRF4 in cultured cells. In contrast, a myoblast determination factor MyoD suppresses the RECK-promoter. Myoblastic cells lacking RECK expression give rise to myotubes at higher efficiency than the cells expressing RECK, indicating that RECK suppresses myotube formation. These findings suggest that MyoD down regulates RECK to facilitate myotube formation, whereas MRF4 up regulates RECK to promote other aspects of myogenesis that require extracellular matrix integrity.