115 RAT EPIDERMAL GROWTH FACTOR GENE EXPRESSION CONTROLLED BY PROGESTERONE DURING PREGNANCY

2008 ◽  
Vol 20 (1) ◽  
pp. 138
Author(s):  
H.-S. Byun ◽  
S.-H. Ko ◽  
G.-S. Lee ◽  
S.-H. Hyun ◽  
E.-B. Jeung
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Uterine Wall ◽  
Mrna Levels ◽  
Heparin Binding ◽  
Pregnant Rats ◽  
Epidermal Growth

The implantation of the developing blastocyst into the uterine wall is regulated by a precisely timed interplay of the ovarian hormones estrogen and progesterone, which control a set of regulatory factors that make the uterus receptive to implantation. These factors include EGF receptor (Egfr) and members of the epidermal growth factor (Egf) family, namely, EGF, heparin-binding EGF (Hbegf), transforming growth factor-alpha (Tgfa), and amphiregulin (Areg). However, the exact role(s) these factors play in pregnancy remain unclear. To address this, a group of three rats was euthanized every day from gestation day (GD) 0 through to GD21. The uterus, attached uterus (these tissues are mostly composed of stromal cells), and placenta were rapidly excised and used directly for total RNA. We used real-time PCR with the TaqMan system (Applied Biosystems, Foster City, CA, ISA) to examine the uterine expression patterns of these factors in rats during the entire pregnancy. Data were analyzed by nonparametric one-way analysis of variance using the Kruskal-Wallis test, followed by Dunnett's test for multiple comparisons. Egf and Egfr mRNA levels increased significantly at implantation, especially on GD3 and GD6, after which their expression gradually decreased. Hbegf and Tgfa showed a modest spike of transcription around the implantation period (GD4 and GD3, respectively) but were much more strongly expressed at mid-pregnancy, which is when progesterone is secreted at high levels. Areg expression peaked strongly around implantation (GD4) and at mid-pregnancy (GD12). Treatment of pregnant rats on GD5 or GD8 with the progesterone receptor antagonist RU486 (2.5 mg per rat) blocked the expression of all of the genes on the days of treatment. Moreover, injection of immature rats with progesterone induced the uterine expression of all of the genes except Hbegf, while injection with estrogen or estrogen plus progesterone had no effect. Taken together, all genes tested may be assumed to regulate the implantation process. Moreover, Hbegf, Tgfa, and Areg may participate during mid-pregnancy. In addition, all of these activities are likely to be controlled by progesterone in the uterus of rats during pregnancy.

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.

174 EPIDERMAL GROWTH FACTORS AND CALBINDIN-D9k GENE EXPRESSIONS DURING PREGANCY IN THE PORCINE UTERUS

2008 ◽  
Vol 20 (1) ◽  
pp. 167
Author(s):  
Y.-J. Kim ◽  
E.-M. Jung ◽  
G.-S. Lee ◽  
S.-H. Hyun ◽  
E.-B. Jeung
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Negative Control ◽  
Heparin Binding ◽  
Gene Expressions ◽  
Calbindin D9k ◽  
Genes Encoding ◽  
Epidermal Growth

To stably maintain pregnancy, several genes are expressed in the uterus. In particular, the endometrial expression of genes encoding growth factors appears to play a key role in maternal–fetal communication. Previous studies have characterized the endometrial expression kinetics of the genes encoding epidermal growth factor (EGF), its receptor (EGFR), transforming growth factor-alpha (TGF-α), amphiregulin (Areg), heparin-binding (Hb) EGF, and calbindin-D9k (CaBP-9k) in the pig during implantation. Here, we further characterized the expression patterns of these molecules during the entire porcine pregnancy. Porcine (n = 3 per PD) were collected at pregnancy days (PD) 12, 15, 30, 60, 90, and 110 and subjected to semi-quantitative RT-PCR. The data were analyzed with a nonparametric one-way analysis of variance using the Kruskal-Wallis test, followed by Dunnett's test for multiple comparisons to the negative control. EGF and EGFR showed similar expression patterns, being highly expressed around implantation time and then disappearing. TGF-α and Areg expression levels rose steadily until they peaked at PD30, after which they gradually decreased to PD12 levels. The Areg mRNA expression pattern was confirmed by real-time PCR, and similar Areg protein expression patterns were observed. Immunohistochemical analysis of PD60 uteri revealed Areg in the glandular and luminal epithelial cells. Hb-EGF was steadily expressed throughout the entire pregnancy while CaBP-9k was expressed strongly on PD12, and then declined sharply in PD15 before recovering slightly for the remainder of the pregnancy. Thus, the EGF family may play a key role during implantation in pigs. In addition, CaBP-9k may help maintain uterine quiescence during pregnancy by sequestering cytoplasmic Ca2+.

scholarly journals Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2385-2392 ◽  
Author(s):  
TM Walz ◽  
C Malm ◽  
BK Nishikawa ◽  
A Wasteson
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Transforming Growth Factor Alpha ◽  
Epidermal Growth ◽  
Factor Alpha

The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.

scholarly journals The Membrane-anchoring Domain of Epidermal Growth Factor Receptor Ligands Dictates Their Ability to Operate in Juxtacrine Mode

2005 ◽  
Vol 16 (6) ◽  
pp. 2984-2998 ◽  
Author(s):  
Jianying Dong ◽  
Lee K. Opresko ◽  
William Chrisler ◽  
Galya Orr ◽  
Ryan D. Quesenberry ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Resonance Energy ◽  
Structural Basis ◽  
Cell Contact ◽  
Heparin Binding ◽  
Epidermal Growth ◽  
Membrane Anchoring

All ligands of the epidermal growth factor (EGF) receptor (EGFR) are synthesized as membrane-anchored precursors. Previous work has suggested that some ligands, such as EGF, must be proteolytically released to be active, whereas others, such as heparin-binding EGF-like growth factor (HB-EGF) can function while still anchored to the membrane (i.e., juxtacrine signaling). To explore the structural basis for these differences in ligand activity, we engineered a series of membrane-anchored ligands in which the core, receptor-binding domain of EGF was combined with different domains of both EGF and HB-EGF. We found that ligands having the N-terminal extension of EGF could not bind to the EGFR, even when released from the membrane. Ligands lacking an N-terminal extension, but possessing the membrane-anchoring domain of EGF, still required proteolytic release for activity, whereas ligands with the membrane-anchoring domain of HB-EGF could elicit full biological activity while still membrane anchored. Ligands containing the HB-EGF membrane anchor, but lacking an N-terminal extension, activated EGFR during their transit through the Golgi apparatus. However, cell-mixing experiments and fluorescence resonance energy transfer studies showed that juxtacrine signaling typically occurred in trans at the cell surface, at points of cell-cell contact. Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode.

scholarly journals The Gene for Heparin-Binding Epidermal Growth Factor-Like Growth Factor is Stress-Inducible: Its Role in Cerebral Ischemia

1999 ◽  
Vol 19 (3) ◽  
pp. 307-320 ◽  
Author(s):  
Nobutaka Kawahara ◽  
Kazuhiko Mishima ◽  
Shigeki Higashiyama ◽  
Naoyuki Taniguchi ◽  
Akira Tamura ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dentate Gyrus ◽  
Transforming Growth Factor ◽  
Adult Brain ◽  
Normal Brain ◽  
Heparin Binding ◽  
Epidermal Growth ◽  
Egf Family

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor-α (TGF-α) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the like-lihood that HB-EGF is a neuroprotective factor in cerebral ischemia.

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