The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors.
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.
Echizenya
Michiko
M
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Japan.
Kondo
Shunya
S
Takahashi
Rei
R
Oh
Junseo
J
Kawashima
Satoshi
S
Kitayama
Hitoshi
H
Takahashi
Chiaki
C
Noda
Makoto
M
D000818:Animals; D015153:Blotting, Western; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; C492025:Reck protein, mouse; C063403:myogenic factor 6; D020782:Matrix Metalloproteinases