|
|
|
|
|
|
|
||
* Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica
Molecolare, Università di Roma La Sapienza, 00161 Roma; and As a rule, hepatocyte growth factor/scatter
factor (HGF/SF) is produced by mesenchymal cells,
while its receptor, the tyrosine kinase encoded by the
met proto-oncogene, is expressed by the neighboring
epithelial cells in a canonical paracrine fashion. In the
present work we show that both HGF/SF and met are
coexpressed by undifferentiated C2 mouse myoblasts.
In growing cells, the autocrine loop is active as the receptor exhibits a constitutive phosphorylation on tyrosine that can be abrogated by exogenously added
anti-HGF/SF neutralizing antibodies. The transcription
of HGF/SF and met genes is downregulated when myoblasts stop proliferating and differentiate. The coexpression of HGF/SF and met genes is not exclusive to
C2 cells since it has been assessed also in other myogenic cell lines and in mouse primary satellite cells, suggesting that HGF/SF could play a role in muscle development through an autocrine way.
To analyze the biological effects of HGF/SF receptor
activation, we stably expressed the constitutively activated receptor catalytic domain (p65tpr-met) in C2 cells.
This active kinase determined profound changes in cell
shape and inhibited myogenesis at both morphological
and biochemical levels. Notably, a complete absence of
muscle regulatory markers such as MyoD and myogenin was observed in p65tpr-met highly expressing C2
clones. We also studied the effects of the ectopic expression of human isoforms of met receptor (h-met) and of HGF/SF (h-HGF/SF) in stable transfected C2 cells.
Single constitutive expression of h-met or h-HGF/SF
does not alter substantially the growth and differentiation properties of the myoblast cells, probably because
of a species-specific ligand-receptor interaction. A C2 clone expressing simultaneously both h-met and
h-HGF/SF is able to grow in soft agar and shows a decrease in myogenic potential comparable to that promoted by p65tpr-met kinase. These data indicate that a
met kinase signal released from differentiation-dependent control provides a negative stimulus for the onset
of myogenic differentiation.
Institute for Cancer Research, Università di Torino, Facoltà di
Medicina, Torino, Italy
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
