scholarly journals Oncogenic Ras-Induced Proliferation Requires Autocrine Fibroblast Growth Factor 2 Signaling in Skeletal Muscle Cells

2001 ◽  
Vol 152 (6) ◽  
pp. 1301-1306 ◽  
Author(s):  
Yuri V. Fedorov ◽  
R. Scott Rosenthal ◽  
Bradley B. Olwin
Keyword(s):  
Skeletal Muscle ◽  
Ectopic Expression ◽  
Terminal Differentiation ◽  
Biological Response ◽  
Muscle Cells ◽  
Sodium Chlorate ◽  
Skeletal Muscle Cells ◽  
Specific Gene ◽  
Fibroblast Growth ◽  
Oncogenic Ras

Constitutively activated Ras proteins are associated with a large number of human cancers, including those originating from skeletal muscle tissue. In this study, we show that ectopic expression of oncogenic Ras stimulates proliferation of the MM14 skeletal muscle satellite cell line in the absence of exogenously added fibroblast growth factors (FGFs). MM14 cells express FGF-1, -2, -6, and -7 and produce FGF protein, yet they are dependent on exogenously supplied FGFs to both maintain proliferation and repress terminal differentiation. Thus, the FGFs produced by these cells are either inaccessible or inactive, since the endogenous FGFs elicit no detectable biological response. Oncogenic Ras-induced proliferation is abolished by addition of an anti–FGF-2 blocking antibody, suramin, or treatment with either sodium chlorate or heparitinase, demonstrating an autocrine requirement for FGF-2. Oncogenic Ras does not appear to alter cellular export rates of FGF-2, which does not possess an NH2-terminal or internal signal peptide. However, oncogenic Ras does appear to be involved in releasing or activating inactive, extracellularly sequestered FGF-2. Surprisingly, inhibiting the autocrine FGF-2 required for proliferation has no effect on oncogenic Ras-mediated repression of muscle-specific gene expression. We conclude that oncogenic Ras-induced proliferation of skeletal muscle cells is mediated via a unique and novel mechanism that is distinct from Ras-induced repression of terminal differentiation and involves activation of extracellularly localized, inactive FGF-2.

Involvement of M-cadherin in terminal differentiation of skeletal muscle cells

1995 ◽  
Vol 108 (9) ◽  
pp. 2973-2981 ◽  
Author(s):  
M. Zeschnigk ◽  
D. Kozian ◽  
C. Kuch ◽  
M. Schmoll ◽  
A. Starzinski-Powitz
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Cell Adhesion ◽  
Troponin T ◽  
Terminal Differentiation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Myogenic Cells ◽  
Calcium Dependent ◽  
Tissue Organization

Cadherins are a gene family encoding calcium-dependent cell adhesion proteins which are thought to act in the establishment and maintenance of tissue organization. M-cadherin, one member of the family, has been found in myogenic cells of somitic origin during embryogenesis and in the adult. These findings have suggested that M-cadherin is involved in the regulation of morphogenesis of skeletal muscle cells. Therefore, we investigated the function of M-cadherin in the fusion of myoblasts into myotubes (terminal differentiation) in cell culture. Furthermore, we tested whether M-cadherin might influence (a) the expression of troponin T, a typical marker of biochemical differentiation of skeletal muscle cells, and (b) withdrawal of myoblasts from the cell cycle (called terminal commitment). The studies were performed by using antagonistic peptides which correspond to sequences of the putative M-cadherin binding domain. Analogous peptides of N-cadherin have previously been shown to interfere functionally with the N-cadherin-mediated cell adhesion. In the presence of antagonistic M-cadherin peptides, the fusion of myoblasts into myotubes was inhibited. Analysis of troponin T revealed that it was downregulated at the protein level although its mRNA was still detectable. In addition, withdrawal from the cell cycle typical for terminal commitment of muscle cells was not complete in fusion-blocked myogenic cells. Finally, expression of M-cadherin antisense RNA reducing the expression of the endogenous M-cadherin protein interfered with the fusion process of myoblasts. Our data imply that M-cadherin-mediated myoblast interaction plays an important role in terminal differentiation of skeletal muscle cells.

scholarly journals Proline Isomerase Pin1 Represses Terminal Differentiation and Myocyte Enhancer Factor 2C Function in Skeletal Muscle Cells

2010 ◽  
Vol 285 (45) ◽  
pp. 34518-34527 ◽  
Author(s):  
Alessandro Magli ◽  
Cecilia Angelelli ◽  
Massimo Ganassi ◽  
Fiorenza Baruffaldi ◽  
Vittoria Matafora ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Terminal Differentiation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

scholarly journals A pRb-independent mechanism preserves the postmitotic state in terminally differentiated skeletal muscle cells

2004 ◽  
Vol 167 (3) ◽  
pp. 417-423 ◽  
Author(s):  
Grazia Camarda ◽  
Francesca Siepi ◽  
Deborah Pajalunga ◽  
Camilla Bernardini ◽  
Rossella Rossi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Synthesis ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Conditional Knockout ◽  
Skeletal Muscle Cells ◽  
Specific Gene ◽  
Pocket Protein ◽  
Independent Mechanism ◽  
Optimal Implementation

In skeletal muscle differentiation, the retinoblastoma protein (pRb) is absolutely necessary to establish definitive mitotic arrest. It is widely assumed that pRb is equally essential to sustain the postmitotic state, but this contention has never been tested. Here, we show that terminal proliferation arrest is maintained in skeletal muscle cells by a pRb-independent mechanism. Acute Rb excision from conditional knockout myotubes caused reexpression of E2F transcriptional activity, cyclin-E and -A kinase activities, PCNA, DNA ligase I, RPA, and MCM2, but did not induce DNA synthesis, showing that pRb is not indispensable to preserve the postmitotic state of these cells. Muscle-specific gene expression was significantly down-regulated, showing that pRb is constantly required for optimal implementation of the muscle differentiation program. Rb-deleted myotubes were efficiently reactivated by forced expression of cyclin D1 and Cdk4, indicating a functionally significant target other than pRb for these molecules. Finally, Rb removal induced no DNA synthesis even in pocket-protein null cells. Thus, the postmitotic state of myotubes is maintained by at least two mechanisms, one of which is pocket-protein independent.

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