scholarly journals The calcium signal for BALB/MK keratinocyte terminal differentiation counteracts epidermal growth factor (EGF) very early in the EGF-induced proliferative pathway.

1988 ◽  
Vol 8 (2) ◽  
pp. 557-563 ◽  
Author(s):  
P P Di Fiore ◽  
J Falco ◽  
I Borrello ◽  
B Weissman ◽  
S A Aaronson
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Lymphoid Cells ◽  
Epidermal Keratinocytes ◽  
Calcium Signal ◽  
High Calcium ◽  
Epidermal Growth

BALB/MK mouse epidermal keratinocytes require epidermal growth factor (EGF) for proliferation and terminally differentiate in response to high calcium concentrations. We show that EGF is an extremely potent mitogen, causing BALB/MK cultures to enter the cell cycle in a synchronous manner associated with a greater than 100-fold increase in DNA synthesis. Analysis of the expression of proto-oncogenes which have been reported to be activated during the cascade of events following growth factor stimulation of fibroblasts or lymphoid cells revealed a very rapid but transient 100-fold increase in c-fos RNA but little or no effect on the other proto-oncogenes analyzed. Exposure of EGF-synchronized BALB/MK cells to high levels of calcium was associated with a striking decrease in the early burst of c-fos RNA as well as the subsequent peak of cell DNA synthesis. Since the inhibitory effect of high calcium on c-fos RNA expression was measurable within 30 min, our studies imply that the EGF proliferative and calcium differentiation signals must interact very early in the pathway of EGF-induced proliferation. Our results also establish that c-fos RNA modulation is an important early marker of cell proliferation in epithelial as well as mesenchymal cells.

The calcium signal for BALB/MK keratinocyte terminal differentiation counteracts epidermal growth factor (EGF) very early in the EGF-induced proliferative pathway

1988 ◽  
Vol 8 (2) ◽  
pp. 557-563
Author(s):  
P P Di Fiore ◽  
J Falco ◽  
I Borrello ◽  
B Weissman ◽  
S A Aaronson
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Lymphoid Cells ◽  
Epidermal Keratinocytes ◽  
Calcium Signal ◽  
High Calcium ◽  
Epidermal Growth

BALB/MK mouse epidermal keratinocytes require epidermal growth factor (EGF) for proliferation and terminally differentiate in response to high calcium concentrations. We show that EGF is an extremely potent mitogen, causing BALB/MK cultures to enter the cell cycle in a synchronous manner associated with a greater than 100-fold increase in DNA synthesis. Analysis of the expression of proto-oncogenes which have been reported to be activated during the cascade of events following growth factor stimulation of fibroblasts or lymphoid cells revealed a very rapid but transient 100-fold increase in c-fos RNA but little or no effect on the other proto-oncogenes analyzed. Exposure of EGF-synchronized BALB/MK cells to high levels of calcium was associated with a striking decrease in the early burst of c-fos RNA as well as the subsequent peak of cell DNA synthesis. Since the inhibitory effect of high calcium on c-fos RNA expression was measurable within 30 min, our studies imply that the EGF proliferative and calcium differentiation signals must interact very early in the pathway of EGF-induced proliferation. Our results also establish that c-fos RNA modulation is an important early marker of cell proliferation in epithelial as well as mesenchymal cells.

scholarly journals DNA synthesis by ovine mammary alveolar epithelial cells: effects of heparin, epidermal growth factor-related peptides and interaction with stage of pregnancy

1998 ◽  
Vol 156 (2) ◽  
pp. 283-290 ◽  
Author(s):  
IA Forsyth ◽  
JA Taylor ◽  
CD Moorby
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Dna Synthesis ◽  
Cell Cultures ◽  
Inhibitory Effect ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Pregnant Sheep ◽  
Epidermal Growth

Amphiregulin is a heparin-binding member of the epidermal growth factor (EGF) family, which we have recently shown to be expressed in sheep mammary gland. Uniquely among known EGF-like growth factors, its mitogenic activity is inhibited by soluble heparin, but heparin-like molecules on the cell surface and/or in extracellular matrix appear to be necessary for amphiregulin to exert its biological effect. In primary cultures of sheep mammary alveolar epithelial cells, heparin (1-20 mg/l) inhibited DNA synthesis in a dose-dependent manner. The extent of the inhibition was influenced by physiological state, being greater (P < 0.05) in mammary cell cultures derived from 5- to 10-week pregnant sheep (63.1 +/- 8.2%, mean +/- S.E.M., n = 8) than in cultures derived from sheep which were non-pregnant (35.8 +/- 8.3% inhibition, n = 6) or late, 20-week, pregnant (39.8 +/- 5.6%, n = 6). Both EGF and transforming growth factor-alpha (TGF-alpha) significantly (P < 0.001) increased DNA synthesis in the presence of heparin. The effect of TGF-alpha was dose-related, wholly reversing the inhibitory effect of heparin in cell cultures from non-pregnant and 20-week pregnant sheep. DNA synthesis was stimulated by amphiregulin and TGF-alpha increased the maximum response. The heparin antagonist, hexadimethrine, inhibited DNA synthesis, but, in the presence of amphiregulin, approximately equivalent concentrations of heparin overcame this inhibitory effect. In the presence of heparin, TGF-alpha showed synergistic interactions with insulin or IGF-I. The results indicate interactive effects of EGF and IGF growth factor families in sheep mammary growth.

Aging: altered responsiveness of gastric mucosa to epidermal growth factor

1989 ◽  
Vol 257 (4) ◽  
pp. G554-G560 ◽  
Author(s):  
A. P. Majumdar ◽  
F. L. Arlow
Keyword(s):  
Growth Factor ◽  
Gastric Mucosa ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Membrane Fraction ◽  
Kinase Activity ◽  
Thymidine Kinase Activity ◽  
Epidermal Growth ◽  
K Activity

The present investigation examines the responsiveness of the gastric mucosa to the growth-promoting action of epidermal growth factor (EGF) during advancing age. Two sets of experiments were performed. In the first set of experiments, groups of 4-, 8-, 16-, and 24-mo-old Fischer 344 rats were injected subcutaneously at 12-h intervals for 2 days with either EGF (10 micrograms/kg) in gelatin or the vehicle only (controls). The animals were killed 16-18 h after the last injection. The oxyntic gland mucosa was assayed for thymidine kinase and the rate of DNA synthesis in vitro (indicators of proliferative activity) as well as for tyrosine kinase (Tyr-k) activity. In control rats, the rate of DNA synthesis and thymidine kinase activity rose steadily between 4 and 24 mo of age. However, whereas Tyr-k activity in the gastric mucosal cytosol changed only marginally with age, activity of the enzyme in the membrane fraction rose steadily between 4 and 16 mo and then increased abruptly. EGF stimulated gastric mucosal DNA synthesis and thymidine kinase activity in 4- to 16-mo-old rats compared with the corresponding controls, but in the 24-mo-old animals, it caused a significant 40-50% inhibition. EGF had no demonstrable effect on Tyr-k activity in either cytosolic or membrane fraction. We postulated that Tyr-k activity might have returned to basal level 16-18 h after the last EGF injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminofluoride- and Epidermal Growth Factor-Stimulated DNA Synthesis in MOB 3-4-F2 Cells

1991 ◽  
Vol 69 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Tomoyuki Kawase ◽  
Michiaki Orikasa ◽  
Akitoshi Suzuki
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Epidermal Growth

Members of the src and ras oncogene families supplant the epidermal growth factor requirement of BALB/MK-2 keratinocytes and induce distinct alterations in their terminal differentiation program

1985 ◽  
Vol 5 (12) ◽  
pp. 3386-3396
Author(s):  
B Weissman ◽  
S A Aaronson
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Terminal Differentiation ◽  
Epidermal Keratinocytes ◽  
Ras Oncogene ◽  
Rapid Loss ◽  
Naturally Occurring ◽  
Epidermal Growth ◽  
Transforming Genes ◽  
Mouse Epidermal Keratinocytes

BALB-/MK-2 mouse epidermal keratinocytes required epidermal growth factor for proliferation and terminally differentiated in response to high Ca2+ concentration. Infection with retroviruses containing transforming genes of the src and ras oncogene families led to rapid loss of epidermal growth factor dependence, in some cases, accompanied by alterations in cellular morphology. The virus-altered cells continued to proliferate in the presence of high levels of extracellular calcium but exhibited alterations in normal keratinocyte terminal differentiation that appear to be specific to the particular oncogene. These alterations bore similarities to abnormalities in differentiation observed in naturally occurring squamous epithelial malignancies.

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