Tissue-specific effects of castration and ovariectomy on murine epidermal growth factor and its mRNA

1989 ◽  
Vol 121 (3) ◽  
pp. 501-506 ◽  
Author(s):  
J. C. Pascall ◽  
J. Saunders ◽  
D. M. Blakeley ◽  
M. S. Laurie ◽  
K. D. Brown
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Submaxillary Gland ◽  
Mrna Levels ◽  
Maximal Increase ◽  
Control Female ◽  
Tissue Specific ◽  
Epidermal Growth ◽  
Low Levels

ABSTRACT The polypeptide mitogen, epidermal growth factor (EGF), was originally isolated from mouse submaxillary gland (SMG). In mice, these glands are sexually dimorphic; the SMG of male animals typically contains up to 400 pmol EGF/mg protein whereas EGF concentrations in the SMG of female mice are only 5–20 pmol/mg protein. When mice were castrated at 8 weeks of age, EGF mRNA levels in the SMG fell rapidly to the low levels observed in control female animals. Although the concentration of EGF in the SMG, measured by radioimmunoassay, also fell to very low levels (13·8 ± 0·7 (s.e.m.) pmol/mg protein) in the castrated mice, the rate of decrease was considerably slower than that of the mRNA. In contrast to the loss of EGF and EGF mRNA from mice following castration, ovariectomy led to a rise in EGF mRNA levels in SMG, with a maximal increase (approximately 100-fold) 4–6 weeks after ovariectomy. Concentrations of EGF in the SMG also rose markedly in the ovariectomized animals, from a control value of 5·4 ± 0·8 to 34·7 ± 7·9 pmol/mg protein at 6 weeks. In mice, the kidney displays the second highest level of EGF gene expression. However, in contrast to the effects on SMG, kidney EGF mRNA was not affected by either castration or ovariectomy. These results provide further evidence for the tissue-specific control of EGF gene expression in response to steroid hormones. Journal of Endocrinology (1989) 121, 501–506

scholarly journals Epidermal growth factor and phorbol myristate acetate increase expression of the mRNA for cytosolic phospholipase A2 in glomerular mesangial cells

1993 ◽  
Vol 295 (3) ◽  
pp. 763-766 ◽  
Author(s):  
A P Maxwell ◽  
H J Goldberg ◽  
A H N Tay ◽  
Z G Li ◽  
G S Arbus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase A2 ◽  
Mesangial Cells ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Pla2 Activity ◽  
Mrna Accumulation ◽  
Epidermal Growth

We have previously shown that phospholipase A2 (PLA2) activity is rapidly activated by epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA) in renal mesangial cells and other cell systems in a manner that suggests a covalent modification of the PLA2 enzyme(s). This PLA2 activity is cytosolic (cPLA2) and is distinct from secretory forms of PLA2, which are also stimulated in mesangial cells in response to cytokines and other agonists. However, longer-term regulation of cPLA2 in renal cells may also occur at the level of gene expression. Cultured rat mesangial cells were used as a model system to test the effects of EGF and PMA on the regulation of cPLA2 gene expression. EGF and PMA both produced sustained increases in cPLA2 mRNA levels, with a parallel increase in enzyme activity over time. Inhibition of protein synthesis by cycloheximide increased basal cPLA2 mRNA accumulation in serum-starved mesangial cells, and the combination of EGF and cycloheximide resulted in super-induction of cPLA2 gene expression compared with EGF alone. Actinomycin D treatment entirely abrogated the effect of EGF on cPLA2 mRNA accumulation. These findings suggest that regulation of cPLA2 is achieved by factors controlling gene transcription and possibly mRNA stability, in addition to previously characterized posttranslational modifications.

Modulation of epidermal growth factor binding and receptor gene expression by hormones and growth factors in sheep pituitary cells

1994 ◽  
Vol 143 (3) ◽  
pp. 489-496 ◽  
Author(s):  
S S Chaidarun ◽  
M C Eggo ◽  
P M Stewart ◽  
M C Sheppard
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Receptor Gene ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
High Affinity ◽  
Epidermal Growth ◽  
Receptor Gene Expression

Abstract Epidermal growth factor (EGF) is a potent mitogen for sheep pituitary cells but the factors controlling the binding and expression of EGF and its receptor (EGFR) in the pituitary are poorly understood. Regulation of EGF binding and EGFR gene expression may determine cellular responsiveness to EGF and could play a role in neoplastic development. Scatchard analysis of 125I-EGF binding in cultured sheep pituitary cells revealed two receptor binding sites (high affinity class of 2·5± 0·5 × 103 receptors/cell with a dissociation affinity constant (Kd) of 3·2± 0·7 × 1010m and low affinity class of 3·3 ±1·0 × 104 receptors/cell with a Kd of 71 ±1·3 × 10−9 m). Exposure of the cultured cells to some target gland hormones of the pituitary (oestrogen, tri-iodothyronine and hydrocortisone), pituitary growth factors (EGF, basic fibroblast growth factor, transforming growth factor-β and a tumour-promoting phorbol ester (TPA) resulted in an increase in the binding affinity of the high affinity receptors while reducing the receptor number and also a reduction of EGFR mRNA levels, shown by Northern blot analysis. In contrast, forskolin, an activator of adenylate cyclase, showed no significant effect on EGF binding and receptor gene expression. We conclude that the EGFR in normal pituitary cells can be modulated by several hormones and other growth factors at both receptor binding and mRNA levels. Transmodulation of EGFR by hormones and growth factors in the pituitary may be one of the regulatory mechanisms controlling the balance of normal pituitary growth and function. Defects in this regulatory system could have a role in the multistep process of pituitary tumourigenesis. Journal of Endocrinology (1994) 143, 489–496

The epidermal growth factor receptor ligand amphiregulin is a negative regulator of hepatic acute-phase gene expression

2009 ◽  
Vol 51 (6) ◽  
pp. 1010-1020 ◽  
Author(s):  
Ana Pardo-Saganta ◽  
Maria Ujue Latasa ◽  
Josefa Castillo ◽  
Laura Alvarez-Asiain ◽  
María J. Perugorría ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Acute Phase ◽  
Growth Factor Receptor ◽  
Negative Regulator ◽  
Receptor Ligand ◽  
Epidermal Growth

Emergence of salivary gland cell lineage diversity suggests a role for androgen-independent epidermal growth factor receptor signaling

1995 ◽  
Vol 108 (6) ◽  
pp. 2205-2212
Author(s):  
E.M. Durban ◽  
P.G. Nagpala ◽  
P.D. Barreto ◽  
E. Durban
Keyword(s):  
Salivary Gland ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Cell Lineage ◽  
Mrna Levels ◽  
Receptor Signaling ◽  
Receptor Mrna ◽  
Epidermal Growth ◽  
Lineage Diversity

Diversity of cell lineages within glandular organs is generated postnatally by differentiation of committed progenitor cells. Fundamental regulatory aspects of this process are not understood. The mouse submandibular salivary gland (SSG) served as model to assess the role of epidermal growth factor (EGF) receptor signaling during emergence of cell lineage diversity. Temporal fluctuations in EGF receptor mRNA levels coincident with crucial differentiative cell lineage transitions were revealed by RNase protection analyses. Between days 2 and 5, when proacinar cells are maturing and striated duct cells emerge, EGF receptor mRNA levels were highest and all differentiating cells exhibited EGF receptor immunoreactivity. EGF receptor mRNA levels then declined sharply and immunoreactivity became confined to ductal cells. At day 11 in male mice, and days 11 and 16 in females, a second increase in EGF receptor mRNA was detected coincident with emergence of granular convoluted tubule (GCT) cells. With completion of androgen-dependent GCT cell differentiation at the onset of puberty, EGF receptor mRNA levels and intensity of immunoreactivity decreased. Androgen effects on EGF receptor mRNA or immunoreactivity could not be detected. These temporally distinct patterns of EGF receptor expression suggest that this signaling pathway is a mechanism of potential importance in emergence of cell lineage diversity in a glandular organ.

scholarly journals Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis

1999 ◽  
Vol 277 (4) ◽  
pp. L684-L693 ◽  
Author(s):  
Christine L. Zanella ◽  
Cynthia R. Timblin ◽  
Andrew Cummins ◽  
Michael Jung ◽  
Jonathan Goldberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Direct Interaction ◽  
Mrna Levels ◽  
Binding Studies ◽  
Therapeutic Implications ◽  
Asbestos Fibers ◽  
Epidermal Growth

We examined the mechanisms of interaction of crocidolite asbestos fibers with the epidermal growth factor (EGF) receptor (EGFR) and the role of the EGFR-extracellular signal-regulated kinase (ERK) signaling pathway in early-response protooncogene (c- fos/c- jun) expression and apoptosis induced by asbestos in rat pleural mesothelial (RPM) cells. Asbestos fibers, but not the nonfibrous analog riebeckite, abolished binding of EGF to the EGFR. This was not due to a direct interaction of fibers with ligand, inasmuch as binding studies using fibers and EGF in the absence of membranes showed that EGF did not adsorb to the surface of asbestos fibers. Exposure of RPM cells to asbestos caused a greater than twofold increase in steady-state message and protein levels of EGFR ( P < 0.05). The tyrphostin AG-1478, which inhibits the tyrosine kinase activity of the EGFR, but not the tyrphostin A-10, which does not affect EGFR activity, significantly ameliorated asbestos-induced increases in mRNA levels of c- fos but not of c- jun. Pretreatment of RPM cells with AG-1478 significantly reduced apoptosis in cells exposed to asbestos. Our findings suggest that asbestos-induced binding to EGFR initiates signaling pathways responsible for increased expression of the protooncogene c- fos and the development of apoptosis. The ability to block asbestos-induced elevations in c- fos mRNA levels and apoptosis by small-molecule inhibitors of EGFR phosphorylation may have therapeutic implications in asbestos-related diseases.

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