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)

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

Nuclear steroid/thyroid/retinoid receptors and c-erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c-erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross-connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c-erbB-2, and between ER and retinoic acid receptor(RAR)-alpha have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12-O-tetradecanoylphorbol-13-acetate, TPA), on growth and expression of c-erbB and RARs in MCF-7 breast cancer cells, which contain high levels of RAR-alpha and -gamma, and which express significant amounts of c-erbB-2 and -3. All trans-retinoic acid (tRA), the anti-estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17beta-estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c-erbB-2 and -3, whereas tamoxifen, Forsk and TPA up-regulated c-erbB-2. c-erbB-3 was co-regulated with c-erbB-2. Northern analysis demonstrated that RAR-alpha was down-regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up-regulated RAR-alpha. RAR-gamma expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c-erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.
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PMID:Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c-erbB and retinoic acid receptor expression in MCF-7 breast cancer cells. 1067 83

Apart from the regulation of calcium metabolism, 1, 25-dihydroxyvitamin D(3) plays an essential role in cell proliferation and differentiation in several tissues. The vitamin D receptor (VDR) gene shows polymorphisms in humans that appear to be clinically significant in some pathological conditions. In the present study, the BsmI polymorphism of the VDR gene was studied in 59 Caucasian patients with rectal cancer (mean follow-up: 48 months). The relationship between VDR genotypes and the expression of oncogenes as well as their influence on survival were also investigated. VDR polymorphism was examined in tumor and normal mucosa cells by PCR technique. The expression of erbB-2/HER-2, p53, ras and epidermal growth factor receptor (EGFR) was also detected by immunohistochemistry and protein blotting. The presence of the VDR B allele significantly correlated with the overexpression of the erbB-2 oncogene. There was no difference in the VDR genotype between cancer and normal mucosal cells. Coexpression of erbB-2, pan-ras, p53 and EGFR internal and external domains was significantly higher in cancer cells than in normal mucosa. There was no significant correlation between VDR genotypes and age, gender, tumor infiltration depth, number and site of lymph node metastases and lymphatic or blood vessel infiltration. The VDR genotype alone did not influence survival. Overexpression of erbB-2 and EGFR was associated with a poor prognosis. In patients expressing only one oncogene in cancer cells, the presence of the VDR B allele showed a tendency to a poor prognosis. In conclusion, VDR gene BsmI polymorphism might affect the development and prognosis of rectal cancer by influencing erbB-2 oncogene expression.
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PMID:Vitamin D receptor gene BsmI polymorphism correlates with erbB-2/HER-2 expression in human rectal cancer. 1076 27

In this study, the Xbal polymorphisms of the estrogen-, the Bsml polymorphism of the vitamin D- as well as the A986S polymorphism of the calcium-sensing receptor genes were investigated in 56 patients with colorectal cancer. The expression of erbB-2, epidermal growth factor receptor, ras, p53 and their relationship to estrogen-, vitamin D- and calcium-sensing receptor genotypes were also studied. In subjects exhibiting XX genotype of the estrogen receptor gene or bb genotype of the vitamin D receptor gene, erbB-2 expression was significantly lower compared to those with xx, Xx or BB, Bb (6/56 and 11/56 vs. 31/56 and 26/56; p = 0.0043 and 0.041). The presence of the XX alleles of estrogen receptor gene significantly correlated with the overexpression of the epidermal growth factor receptor expression in tumors, whereas in xx and Xx genotypes, significantly higher expression was seen (7/56 vs. 30/56; p = 0.049). Analyzing the combinations of the two gene allelic variants, we have found XXbb genotype to be associated with a significantly lower erbB-2 expression, compared to other combinations (Xxbb, XxBb, XXBb) (2/7 vs. 7/7, 4/5, 4/5; p = 0.0011). Patients with AA calcium-sensing receptor genotype were in higher UICC stages at the time of discovery of their disease than those with AS genotype. The AA allelic variant of the calcium-sensing gene was more frequent among patients with colorectal cancer compared to controls (36/56 vs. 36/112; p = 0.0004). Our observations raise the possibility that estrogen-, and vitamin D receptor gene polymorphisms accompanied with variable oncogene expression might influence the pathogenic processes resulting in the development of colorectal cancer. The A986S polymorphism of calcium-sensing receptor might also be a prognostic marker of the disease.
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PMID:[The role of estrogen receptor, vitamin D receptor and calcium receptor genotypes in the pathogenesis of colorectal cancer]. 1139 75

Oestrogen/oestrogen receptor (ER) and vitamin D/vitamin D receptor (VDR) systems have been implicated in the pathogenesis of colorectal cancers. The expression of erbB-2 and epidermal growth factor receptor (EGFR) in colorectal cancers has been suggested to have diagnostic and prognostic significance. In our study, XbaI and PvuII polymorphisms of the ER gene and the BsmI polymorphism of the VDR gene were studied in 56 Caucasian patients with rectal cancer. The relationship between the ER and VDR genotypes and the expression of oncogenes was also investigated. The presence of the x allele of ER gene significantly correlated with the overexpression of the erbB-2 and EGFR oncogenes. Significantly increased erbB-2 expression was observed in patients with the VDR B allele. The XXbb allelic combination of the ER/VDR genes was associated with a significantly lower erbB-2 expression, whereas in the other genotypes significantly higher oncogene expression was seen. Our data raise the possibility that ER/VDR gene polymorphisms accompanied by variable oncogene expression might influence the pathogenetic processes of colorectal cancers.
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PMID:Oestrogen and vitamin D receptor (VDR) genotypes and the expression of ErbB-2 and EGF receptor in human rectal cancers. 1150 51