Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
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PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

The erbB receptor family consists of erbB1/epidermal growth factor receptor, erbB2/neu, erbB3, and erbB4, all of which have been implicated in cell proliferation, differentiation, and survival in several tissues. In the nervous system, these family members can function in a trophic capacity for certain subpopulations of neurons and some types of non-neuronal cells. Vestibular sensory epithelial cells and vestibular ganglion neurons are derived from ectodermal otic placode and are essential components of the peripheral vestibular system, the sensory system for balance. Recent studies in mammals suggest that certain ligands of the epidermal growth factor receptor can induce proliferation of vestibular sensory epithelial cells. We now show that vestibular ganglion neurons and vestibular sensory epithelial cells express all four erbB receptors in adult rats. Cultured vestibular ganglion neurons also expressed all four erbB family members and were therefore used to analyze the effects of modulating erbB signaling on differentiated vestibular ganglion neurons. Transforming growth factor-alpha (a ligand for epidermal growth factor receptor) and sensory and motor neuron-derived factor (a ligand for erbB3 and erbB4) promoted vestibular ganglion neuron viability, whereas epidermal growth factor (another ligand for epidermal growth factor receptor) did not. Glial growth factor 2 (another ligand for erbB3 and erbB4) and an antibody that blocks erbB2/neu-mediated signaling inhibited vestibular ganglion neuron viability. Collectively, these observations indicate that erbB signaling regulates the viability of differentiated otic placode-derived cells in mammals and suggest that exogenous modulation of erbB signaling in peripheral vestibular tissues may prove therapeutically useful in peripheral vestibular disorders.
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PMID:Adult rat otic placode-derived neurons and sensory epithelium express all four erbB receptors: a role in regulating vestibular ganglion neuron viability. 1144 2