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The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors

Oncogene volume 24, pages 5850–5857 (2005)Cite this article

Abstract

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.

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Acknowledgements

We thank Drs Shigeyoshi Itohara and Motoharu Seiki for providing MMP-deficient mice, Drs Harold Weintraub, Stephen F Konieczny, Jeong Yoon, Yoichi Nabeshima, and Woodring E Wright for providing MRF cDNAs, and Ms Mari Kojima for the advise on histological techniques. This work was supported by grants from MEXT, Japan.

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Authors and Affiliations

  1. Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, 606-8501, Kyoto, Japan

    Michiko Echizenya, Shunya Kondo, Junseo Oh, Satoshi Kawashima, Hitoshi Kitayama, Chiaki Takahashi & Makoto Noda

  2. Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, 606-8501, Kyoto, Japan

    Shunya Kondo

  3. Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, 606-8507, Kyoto, Japan

    Rei Takahashi

  4. Korea University Graduate School of Medicine, Ansan, Korea

    Junseo Oh

  5. COE Program, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, 606-8501, Kyoto, Japan

    Chiaki Takahashi

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  1. Michiko Echizenya
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  2. Shunya Kondo
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Correspondence to Makoto Noda.

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Echizenya, M., Kondo, S., Takahashi, R. et al. The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors. Oncogene 24, 5850–5857 (2005). https://doi.org/10.1038/sj.onc.1208733

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