Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 13-cis retinoic acid (RA) and dexamethasone on the levels of epidermal growth factor (EGF) receptor and fibroblast derived proteoglycan core protein (PG40) mRNAs were studied in human skin fibroblasts. The EGF receptor is involved in the regulation of cellular proliferation and the synthesis of matrix proteins, and proteoglycan 40 is important for cell attachment and interaction with collagen and fibronectin. 13-cis-RA at a concentration of 10(-7) M markedly reduced the levels of the EGF receptor and PG40 mRNAs, the decreases being 33 and 56%, respectively. Dexamethasone reduced these mRNAs markedly less. Simultaneous treatment of the fibroblasts with 13-cis-RA and dexamethasone resulted in similar decreases in EGF receptor and PG40 mRNAs as with 13-cis-RA alone. Surprisingly, the proliferation rate of the fibroblasts was increased in the presence of dexamethasone under conditions similar to those which caused slight decrease in the EGF receptor mRNA levels. This indicates that glucocorticoids also affect the cellular growth by mechanisms which do not involve EGF receptors.
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PMID:13-cis retinoic acid and dexamethasone modulate the gene expression of epidermal growth factor receptor and fibroblast proteoglycan 40 core protein in human skin fibroblasts. 257 17

We have investigated the actions of transforming growth factor (TGF) type alpha on epidermal growth factor (EGF) receptor mRNA expression in MDA-468 human mammary carcinoma cells in serum-free media. We found that exposure of MDA-468 cells to TGF alpha results in elevated levels of EGF receptor mRNA. This increase in mRNA accumulation showed time and dose dependence. Addition of TGF beta 1 enhanced the accumulation of EGF receptor mRNA induced by TGF alpha in a time- and dose-dependent manner. We also found that triiodothyronine at physiological concentrations exerts synergistic control on the action of TGF alpha alone, or in association with TGF beta 1, on EGF receptor mRNA expression. Similarly, retinoic acid treatment also enhanced in a time- and dose-dependent manner the TGF alpha-dependent response of EGF receptor mRNA and acted synergistically with TGF beta 1. The results described here suggest that optimum regulation of EGF receptor gene expression by TGF alpha is a complex process involving synergistic interactions with heterologous growth factors and hormones.
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PMID:Modulation of transforming growth factor alpha-dependent expression of epidermal growth factor receptor gene by transforming growth factor beta, triiodothyronine, and retinoic acid. 261 50

The effects of retinoic acid on the epidermal growth factor (EGF) receptor binding and cell growth of normal and simian virus 40 (SV40)-transformed BALB/c 3T3 cells were compared under identical culture conditions. Retinoic acid induced a rapid enhancement of EGF binding to SV40-transformed cells. Half-maximal enhancement occurred at about 7 h after the cells were exposed to 20 ng/ml of retinoic acid, and maximal stimulation (from 2.5- to 3.5-fold over the control) was obtained after 12 h of exposure. The kd of the control and retinoic acid-treated cells was calculated to be 8.0 X 10(-10) M and 8.2 X -10 M, respectively. However, the number of unoccupied EGF binding sites increased from 0.98 X 10(4) to 2.28 X 10(4) per cell. Normal 3T3 cells would not respond to retinoic acid unless they were cultured in serum-containing medium. After 96 h of exposure, only a 50% enhancement of EGF binding was observed. The EGF receptor number of the untreated normal cells was calculated to be 1.82 X 10(4) per cell, twice the number expressed by untreated SV40-transformed cells. The increase of EGF receptor number caused by retinoic acid in SV40-transformed cells was blocked by either actinomycin D or cycloheximide treatment. These results indicated that SV40 transformation of BALB/c 3T3 cells altered the regulatory mechanism governing the complement of cell surface EGF receptors.
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PMID:Differential responsiveness of normal and simian virus 40-transformed BALB/c 3T3 cells to retinoic acid: rapid enhancement of epidermal growth factor receptor binding in a simian virus 40-3T3 variant. 304 Feb 36

Among the tissue, cellular, and molecular changes which take place during the development of squamous cell carcinoma (SCC) of the upper aerodigestive tract, only a limited number can be used as surrogate endpoint biomarkers (SEBs) in cancer chemoprevention trials. Molecular SEBs will be genes or gene products which can be measured accurately and reliably, are altered in intraepithelial neoplasia (dysplasia), correlate strongly with the true outcome (invasive cancer), and are modulated by a chemoprevention agent(s). To identify and modulate molecular SEBs in intraepithelial neoplasia of the upper aerodigestive tract, we studied expression of the epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), and HER-2/neu genes in oral leukoplakia before, during, and after treatment with 13-cis-retinoic acid, a vitamin A derivative. Four of nine patients treated for 3 months with 1 mg/kg/day of 13-cis-retinoic acid had complete resolution of their leukoplakia. Biopsies were taken of leukoplakia and adjacent normal-appearing mucosa before, during, and after treatment. Immunohistochemistry was performed using the BioGenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system. Pretreatment expression of EGFR, TGF-alpha, and HER-2/neu in leukoplakia was increased when compared to normal-appearing mucosa. TGF-alpha expression decreased during treatment in leukoplakia, but not in normal-appearing mucosa, suggesting that TGF-alpha may serve as an intermediate endpoint in cancer chemoprevention trials.
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PMID:Retinoid modulation of biomarkers in oral leukoplakia/dysplasia. 782

Vitamin A is an important factor during gestation and its metabolite, retinoic acid (RA), is a potent teratogen. However, RA action on the placenta is still poorly understood. In this study we analysed the presence of RARs and RXRs in human trophoblastic cells. We determined that RAR alpha was the more expressed form in term placenta, and that RAR beta was induced by RA treatment. Then we analysed RA effects on endocrine activities and on epidermal growth factor (EGF) receptor expression. We found that RA decreased 125I-labeled EGF binding and EGF-dependent phosphorylation. Furthermore, RA treatment led to a concentration-dependent decrease in the amount of EGFR protein expression. This treatment also decreased EGF receptor mRNA levels, suggesting transcriptional regulation of the EGF receptor. Thus we demonstrated that RA could interact with feto-placental development by modulating trophoblast EGF receptors expression, probably via its nuclear receptors.
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PMID:Nuclear retinoic acid receptor characterization in cultured human trophoblast cells: effect of retinoic acid on epidermal growth factor receptor expression. 785 22

Interleukin (IL) 1 alpha induced the up-regulation of cell-surfac-expressed epidermal growth factor (EGF) receptor on both MDA-MB-468 and BT-20 breast cancer cell lines. IL-1 beta and tumor necrosis factor alpha (TNF-alpha) increased the EGF receptor surface expression only on BT-20 breast carcinoma cells. 12-O-tetradecanoylphorbol 13-acetate (TPA) induced up-regulation of EGF receptor on MDA-MB-468 cells, and a marginal but significant increase was determined in BT-20 cells and in interferon gamma (IFN-gamma)-treated MDA-MB-468 cells. CD15 (Lewisx) antigen was down-regulated on MDA-MB-468 cells by TNF-alpha, TPA, IL-1 alpha, as well as by IFN-gamma and all-trans-retinoic acid. 1,25(OH)2-vitamin D3 up-regulated the CD15 antigen surface expression on MDA-MB-468 cells.
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PMID:Modulation of EGF receptor and CD15 (Lewisx) antigen on the cell surface of breast carcinoma cell lines induced by cytokines, retinoic acid, 12-O-tetradecanoylphorbol 13-acetate and 1,25(OH)2-vitamin D3. 790 17

It has previously been shown that, in the estrogen-receptor-positive breast-tumor cell lines T47D and ZR75.1, the erbB-2 protein and mRNA content are controlled negatively and positively by, respectively, estrogens and anti-estrogens. Since estrogens have a positive effect on cell proliferation, while anti-estrogens inhibit cell growth, the results suggested that there may be an inverse correlation between growth and erbB-2 expression. We have now examined this matter further. The effect of various growth-modulatory agents including estrogen (E2), progesterone (Pg), retinoic acid (RA), epidermal growth factor (EGF), insulin (Ins), prolactin (Prl), 12-O-tetradecanolyl-phorbol-13-acetate (TPA) and dibutyryl-3':5'-cyclic-AMP (cAMP) on c-erbB-2 promoter activity, RNA and protein expression have been examined. The growth stimulators E2 and EGF both reduced the level of erbB-2 protein. However, while E2 clearly repressed erbB-2 transcription, in the case of EGF, neither mRNA nor transcription were decreased. Of the agents which inhibit the growth of T47D and ZR75.1 cells--Pg, Prl, cAMP, RA and TPA--only Pg and cAMP caused an increase in the erbB-2 protein level. Pg and cAMP positively influenced c-erbB-2 promoter activity and RNA amount. TPA and RA also increased promoter activity but neither erbB-2 mRNA nor protein level was enhanced. The erbB-2 protein expression in cultures of T47D and ZR75.1 cells at different densities was also analyzed. Both the level of erbB-2 protein and c-erbB-2 promoter activity rose markedly in confluent cultures, suggesting a transcriptional mechanism of control. In conclusion, the data suggest that the effects of various agents on erbB-2 expression are complex and cannot be explained simply as reflecting the growth state of the cells.
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PMID:erbB-2 expression in estrogen-receptor-positive breast-tumor cells is regulated by growth-modulatory reagents. 790 79

Retinoids are potent regulators of epithelial cell growth and differentiation. Recently, they have been demonstrated to be effective in the treatment of preneoplastic cervical lesions in which human papillomavirus (HPV) is expressed. To better understand the mechanism of the antineoplastic effect of retinoic acid on HPV-positive cells, the effects of retinoic acid on both normal and HPV-immortalized human ectocervical epithelial cell growth, epidermal growth factor (EGF) receptor level, and EGF receptor function were investigated. Both HPV-immortalized cells (ECE16-1) and normal ectocervical cells (ECE cells) are growth stimulated by EGF. ECE16-1 but not normal ectocervical epithelial cells are growth inhibited by trans-retinoic acid which attenuates the stimulatory effect of EGF on ECE16-1 cell growth. Retinoic acid reduces both EGF binding and EGF receptor protein levels in ECE16-1 cells but not in normal ectocervical cells. The reduction in EGF receptor binding and receptor protein levels in ECE16-1 cells is not associated with the induced secretion of a soluble EGF receptor ligand, altered EGF receptor affinity, receptor internalization, or decreased receptor stability. Interestingly, the level of EGF receptors is consistently elevated in the ECE16-1 cell line as compared to normal ectocervical epithelial cells. Investigation of a second HPV-immortalized cell line (ECE16-D1) and two other HPV-positive cervical carcinoma cell lines revealed similar elevated EGF-binding capacity and regulation by retinoic acid. In contrast, two HPV-negative cervical carcinoma cell lines demonstrated various EGF-binding levels but demonstrated no significant loss of EGF binding following retinoic acid treatment. Other normal cells and an SV40 large T-antigen-immortalized foreskin keratinocyte cell line, KER-1, had EGF receptor levels similar to the normal ectocervical epithelial cells, and no regulation by retinoic acid was observed. These data indicate that HPV immortalization may increase EGF receptor levels in ectocervical cells, elevating their sensitivity to growth stimulation by EGF, and that retinoic acid can possibly attenuate this increased responsiveness to EGF.
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PMID:Human papillomavirus 16 immortalization of normal human ectocervical epithelial cells alters retinoic acid regulation of cell growth and epidermal growth factor receptor expression. 840 22

The retinoic acid-inducible transcription factor AP-2 is expressed in epithelial and neural crest cell lineages during murine development. AP-2 can regulate neural and epithelial gene transcription, and is associated with overexpression of c-erbB-2 in human breast-cancer cell lines. To ascertain the importance of AP-2 for normal development, we have derived mice containing a homozygous disruption of the AP-2 gene. These AP-2-null mice have multiple congenital defects and die at birth. In particular, the AP-2 knockout mice exhibit anencephaly, craniofacial defects and thoraco-abdominoschisis. Skeletal defects occur in the head and trunk region, where many bones are deformed or absent. Analysis of these mice earlier in embryogenesis indicates a failure of cranial neural-tube closure and defects in cranial ganglia development. We have shown that AP-2 is a fundamental regulator of mammalian craniofacial development.
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PMID:Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2. 862 66

Although osteoblast proliferation is a prominent feature of osteitis fibrosa, studies in vitro using osteoblast-like cells have shown that parathyroid hormone (PTH) impairs cell growth. Recent studies in our laboratory have shown that PTH increases epidermal growth factor (EGF) receptor expression in UMR 106-01 osteoblast-like cells, and thus, osteoblast proliferation may occur as a result of an enhanced response of the osteoblast to EGF. In the present studies we investigated the effect of calcitriol and the influence of retinoids on the regulation of EGF receptors. Calcitriol increased 125I-EGF binding 2.5-3-fold after 72 hours of incubation and was maximal at a calcitriol dose of 100 nM. Scatchard analysis showed that this effect was due to increased receptor number. In contrast, all-trans retinoic acid or 9-cis retinoic acid alone, even at 10 microM, caused less than a 50% increase in 125I-EGF binding. However, the effect of calcitriol was totally abolished in the presence of all-trans retinoic acid. 9-cis retinoic acid was equivalent with all-trans retinoic acid in this regard. In the presence of either retinoid, the stimulatory effect of PTH was totally eliminated and EGF binding was actually decreased below control values. Additional studies revealed that retinoic acid decreased PTH-stimulated cAMP generation in a dose-dependent manner. These data are consistent with our previous studies which showed that the effect of PTH on the induction of EGF receptors was mediated by a cAMP-dependent mechanism. The inhibition of the calcitriol effect by retinoids is consistent with the requirement of the retinoid-X-receptor (RXR) for binding of the vitamin D receptor (VDR) to its target sequences in DNA. These data indicate that EGF receptors in UMR 106-01 cells are up-regulated by PTH and calcitriol and that this process can be modulated by retinoids. Retinoids, therefore, may play a major role in the regulation of osteoblast function by PTH and calcitriol.
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PMID:Retinoids modulate the effect of PTH and calcitriol on EGF receptor expression in UMR 106-01 cells. 866 85


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