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.

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 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.

Epidermal growth factor inhibits Ca(2+)-dependent Cl- transport in T84 human colonic epithelial cells

1996 ◽  
Vol 271 (3) ◽  
pp. C914-C922 ◽  
Author(s):  
J. M. Uribe ◽  
C. M. Gelbmann ◽  
A. E. Traynor-Kaplan ◽  
K. E. Barrett
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Inhibitory Effect ◽  
Inhibitory Pathway ◽  
T84 Cells ◽  
Colonic Epithelial Cells ◽  
Cl Secretion ◽  
Epidermal Growth ◽  
Time Point

This study examined whether epidermal growth factor (EGF) inhibits Ca(2+)-dependent Cl- secretion by T84 cells. Basolateral EGF inhibited Cl- secretion induced by carbachol or thapsigargin, without blocking the rise in intracellular Ca2+. Studies have shown that carbachol renders T84 cells refractory to subsequent stimulation by thapsigargin, an effect ascribed to D-myo-inositol 3,4,5,6-tetrakisphosphate [D-Ins(3,4,5,6)P4]. EGF also increased DL-Ins(3,4,5,6)P4 to a maximum of 170% above control. However, despite the fact that EGF inhibited Cl- secretion at 1 min, DL-Ins(3,4,5,6)P4 was not elevated at this time point. EGF plus carbachol had a greater inhibitory effect on Cl- secretion than either alone, indicating the likely involvement of an additional inhibitory pathway activated by EGF. Staurosporine did not alter the ability of EGF to inhibit Cl- secretion or increase DL-Ins(3,4,5,6)P4. In contrast, genistein inhibited the rise in DL-Ins(3,4,5,6)P4 and partially reversed EGF's inhibitory effect on Cl- secretion. In conclusion, EGF and carbachol can both inhibit Cl- secretion via D-Ins(3,4,5,6)P4, whereas EGF also generates an additional inhibitory signal.

Regulation of epidermal growth factor receptor expression and morphology of lung epithelial cells by interleukin-1β

2020 ◽  
Vol 168 (2) ◽  
pp. 113-123
Author(s):  
Izumi Nakayama ◽  
Sayomi Higa-Nakamine ◽  
Ayako Uehara ◽  
Kazuhiro Sugahara ◽  
Manabu Kakinohana ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Map Kinase ◽  
Morphological Changes ◽  
A549 Cells ◽  
Growth Factor Receptor ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Epidermal Growth

Abstract Accumulating evidences suggested that the overactivation of epidermal growth factor receptor (EGFR) was involved in the development of adult respiratory distress syndrome and pulmonary fibrosis. Elucidation of the mechanisms that regulate EGFR residence on the plasma membrane during inflammatory lung conditions is important for identifying potential therapies. We have demonstrated that flagellin phosphorylated EGFR at Ser1047 and induced transient EGFR internalization. In this study, we examined the molecular pathway and effect of interleukin 1 beta (IL-1β) on EGFR in alveolar epithelial cells. Treatment of A549 cells with IL-1β induced the activation of p38 mitogen-activated protein kinase (MAP kinase) and MAP kinase-activated protein kinase-2 (MAPKAPK-2), as well as EGFR phosphorylation at serine 1047. Both MAPKAPK-2 activation and EGFR phosphorylation were inhibited by SB203580, a p38 MAP kinase inhibitor. In addition, MK2a inhibitor (a MAPKAPK-2 inhibitor) suppressed EGFR phosphorylation. Assessment of the biotinylation of cell surface proteins indicated that IL-1β induced EGFR internalization. Furthermore, long-term treatment of A549 cells with IL-1β caused morphological changes and loss of cell–cell contact. Moreover, IL-1β augmented the effect of transforming growth factor beta 1 on the epithelial–mesenchymal transition. These results suggested that IL-1β regulates EGFR functions and induces morphological changes of alveolar epithelial cells.

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