D. Montarras et al., MUSCLE DIFFERENTIATION - INSULIN-LIKE GROWTH-FACTORS AS POSITIVE MODULATORS OF MYOGENIC REGULATORY GENES, Comptes rendus de l'Academie des sciences. Serie 3, Sciences de la vie, 316(9), 1993, pp. 1029-1031
The contribution of autocrine production of insulin-like growth factor
II (IGFII) to myogenic differentiation was studied in the mouse myoge
nic C2 cells. Permissive C2 cells were stably transfected with a vecto
r generating antisense RNA complementary to IGF RNAs. Our results show
that : (1) accumulation of IGFII mRNA is dramatically decreased (this
mRNA is undetectable by RNA blotting) ; (2) accumulation of MyoD mRNA
also becomes undetectable by RNA blot analysis ; (3) the ability of t
he cells to differentiate, including the activation of myogenin and my
osin genes, is severely compromised ; (4) expression of the MyoD genes
and the ability to differentiate are restored following the addition
of insulin or IGF to the cells. Our observations indicate that the aut
onomous differentiation of myogenic cells requires 'autocrine producti
on of IGF and raise the possibility that IGFII positively regulates ex
pression of the MyoD gene, one of the members of the myogenic regulato
ry factor family.