Somatomedins (insulin-like growth factors), but not growth hormone, are mitogenic for chicken heart mesenchymal cells and act synergistically with epidermal growth factor and brain fibroblast growth factor

We used targeted homologous recombination to disrupt one c-myc gene copy in a diploid fibroblast cell line and found that a twofold reduction in Myc expression resulted in lower exponential growth rates and a lengthening of the G0-to-S-phase transition (M. Shichiri, K. D. Hanson and J. M. Sedivy, Cell Growth Differ. 4:93-104, 1993). Myc is a transcription factor, and the number of target genes whose regulation could result in differential growth rates may be very large. We have approached this problem by examining effects of reduced c-myc expression in three broad areas: (i) secretion of growth factors, (ii) expression of growth factor receptors, and (iii) intracellular signal transduction between Myc and components of the intrinsic cell cycle clock. We have found no evidence that differential medium conditioning can account for the growth phenotypes. Likewise, the expression of receptors for platelet-derived growth factor, epidermal growth factor, basic fibroblast growth factor, and insulin-like growth factor I was the same in diploid and heterozygous cells (platelet-derived growth factor, epidermal growth factor, fibroblast growth factor, and insulin-like growth factor are the sole growth factors required by these cells for growth in serum-free medium). In contrast, expression of cyclin E, cyclin A, and Rb phosphorylation were delayed when quiescent c-myc heterozygous cells were stimulated to enter the cell cycle. Expression of cyclin D1, cyclin D3, and Cdk2 was not affected. The timing of cyclin E induction was the earliest observable effect of reduced Myc expression. Our data indicate that Myc contributes to regulation of proliferation by a cell-autonomous mechanism that involves the modulation of cyclin E expression and, consequently, progression through the restriction point of the cell cycle.

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Transient upregulation of the glial glutamate transporter GLAST in response to fibroblast growth factor, insulin-like growth factor and epidermal growth factor in cultured astrocytes

Journal of Cell Science ◽

10.1242/jcs.114.20.3717 ◽

2001 ◽

Vol 114 (20) ◽

pp. 3717-3725 ◽

Cited By ~ 1

Author(s):

Keiko Suzuki ◽

Yuji Ikegaya ◽

Sigeru Matsuura ◽

Yoshikatsu Kanai ◽

Hitoshi Endou ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Fibroblast Growth Factor ◽

Glutamate Transporter ◽

Insulin Like Growth Factor ◽

Fibroblast Growth ◽

Transport Activity ◽

Glial Glutamate Transporter ◽

Epidermal Growth

Although expression of the glial glutamate transporter GLAST is tightly regulated during development and under pathophysiological conditions, little is known about endogenous modulators of GLAST expression. Because growth factors are generally believed to regulate glial functions, we addressed their possible contribution to GLAST regulation in cultured rat astrocytes. Of the six growth factors tested (basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), insulin, platelet-derived growth factor, and hepatocyte growth factor), bFGF, IGF-1 and EGF enhanced [3H]glutamate transport activity in a concentration-dependent manner. These effects were accompanied by an increase in the Vmax value for transport activity and in GLAST protein and mRNA levels, which suggests that GLAST expression is transcriptionally regulated by the growth factors. Interestingly, the effects reached a peak after 36 hours of exposure to growth factors, and rapidly returned to baseline by 48 hours. A combination of IGF-1 with either bFGF or EGF showed an additive effect on the glutamate uptake activity, but a combination of bFGF and EGF did not. Pharmacological blockade of protein kinase C inhibited the effects of IGF-1 and EGF, but not bFGF. By contrast, genistein, an inhibitor of tyrosine kinases, blocked the effects of bFGF and EGF without affecting the effect of IGF-1. These results suggest that the growth factors activate different signaling pathways for GLAST upregulation. The present study may indicate a novel regulatory system of glial glutamate transporters.

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Effects of c-myc expression on cell cycle progression.

Molecular and Cellular Biology ◽

10.1128/mcb.14.9.5748 ◽

1994 ◽

Vol 14 (9) ◽

pp. 5748-5755 ◽

Cited By ~ 98

Author(s):

K D Hanson ◽

M Shichiri ◽

M R Follansbee ◽

J M Sedivy

Keyword(s):

Cell Cycle ◽

Growth Factors ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Fibroblast Growth Factor ◽

Growth Rates ◽

Cyclin E ◽

Platelet Derived Growth Factor ◽

Fibroblast Growth ◽

Epidermal Growth

We used targeted homologous recombination to disrupt one c-myc gene copy in a diploid fibroblast cell line and found that a twofold reduction in Myc expression resulted in lower exponential growth rates and a lengthening of the G0-to-S-phase transition (M. Shichiri, K. D. Hanson and J. M. Sedivy, Cell Growth Differ. 4:93-104, 1993). Myc is a transcription factor, and the number of target genes whose regulation could result in differential growth rates may be very large. We have approached this problem by examining effects of reduced c-myc expression in three broad areas: (i) secretion of growth factors, (ii) expression of growth factor receptors, and (iii) intracellular signal transduction between Myc and components of the intrinsic cell cycle clock. We have found no evidence that differential medium conditioning can account for the growth phenotypes. Likewise, the expression of receptors for platelet-derived growth factor, epidermal growth factor, basic fibroblast growth factor, and insulin-like growth factor I was the same in diploid and heterozygous cells (platelet-derived growth factor, epidermal growth factor, fibroblast growth factor, and insulin-like growth factor are the sole growth factors required by these cells for growth in serum-free medium). In contrast, expression of cyclin E, cyclin A, and Rb phosphorylation were delayed when quiescent c-myc heterozygous cells were stimulated to enter the cell cycle. Expression of cyclin D1, cyclin D3, and Cdk2 was not affected. The timing of cyclin E induction was the earliest observable effect of reduced Myc expression. Our data indicate that Myc contributes to regulation of proliferation by a cell-autonomous mechanism that involves the modulation of cyclin E expression and, consequently, progression through the restriction point of the cell cycle.

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