ROLE OF INSULIN-LIKE GROWTH-FACTORS AND MYOGENIN IN THE ALTERED PROGRAM OF PROLIFERATION AND DIFFERENTIATION IN THE NFB4 MUTANT MUSCLE-CELL LINE

被引:22
作者
SARBASSOV, DD
STEFANOVA, R
GRIGORIEV, VG
PETERSON, CA
机构
[1] UNIV ARKANSAS MED SCI HOSP,MCCLELLAN VET HOSP,CTR GERIATR RES EDUC & CLIN,DEPT MED,LITTLE ROCK,AR 72205
[2] UNIV ARKANSAS MED SCI HOSP,MCCLELLAN VET HOSP,CTR GERIATR RES EDUC & CLIN,LITTLE ROCK,AR 72205
关键词
D O I
10.1073/pnas.92.24.10874
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In the present study we used the mutant muscle cell line NFB4 to study the balance between proliferation and myogenic differentiation. We show that removal of serum, which induced the parental C2C12 cells to withdraw from the cell cycle and differentiate, had little effect on NFB4 cells, Gene products characteristic of the proliferative state, such as c-Jun, continued to accumulate in the mutant cells in low serum, whereas those involved in differentiation, like myogenin, insulin like growth factor II (IGF-II), and IGF-binding protein 5 (IGFBP-5) were undetectable, Moreover, NFB4 cells displayed a unique pattern of tyrosine phosphorylated proteins, especially in low serum, suggesting that the signal transduction pathway(s) that controls differentiation is not properly regulated in these cells, Treatment of NFB4 cells with exogenous IGF-I or IGF-II at concentrations shown, to promote myogenic differentiation in wild-type cells resulted in activation of myogenin but not MyoD gene expression, secretion of IGFBP-5, changes in tyrosine phosphorylation, and enhanced myogenic differentiation. Similarly, transfection of myogenin expression constructs also enhanced differentiation and resulted in activation of IGF-II expression, showing that myogenin and IGF-II cross-activate each other's expression. However, in both cases, the expression of Jun mRNA remained elevated, suggesting that IGFs and myogenin cannot overcome all aspects of the block to differentiation in NFB4 cells.
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页码:10874 / 10878
页数:5
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