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 HC11 mouse mammary epithelial cell line has proven to be a valuable in vitro model to study the roles of peptide factors and hormones involved in the growth and differentiation of mammary cells. Treatment of HC11 cells with the lactogenic hormones, dexamethasone, insulin, and PRL (DIP), leads to cellular differentiation and production of the milk protein beta-casein. We have analyzed the effects of Neu differentiation factor (NDF)/heregulin, a newly described activating ligand for erbB-2 and other members of the epidermal growth factor (EGF) receptor family, on cell growth and the expression of milk proteins in HC11 cells. In these cells, NDF induces tyrosine phosphorylation of erbB-2 and erbB-3. Both NDF and EGF stimulate HC11 cell proliferation and promote the responsiveness of HC11 cells to lactogenic hormones. NDF induces the expression of a 22-kilodalton milk protein. This protein is up-regulated by other factors, including dexamethasone, EGF, and basic fibroblast growth factor, and is controlled in a manner distinct from that of beta-casein. Like EGF, NDF inhibits the DIP-induced expression of beta-casein at the level of transcription. The inhibition is due to the negative effect of NDF on the activation of mammary gland factor (MGF/Stat5), a member of the Stat family of transcription factors, which is essential for beta-casein gene expression.
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PMID:Neu differentiation factor/heregulin modulates growth and differentiation of HC11 mammary epithelial cells. 776 Aug 47

Recent data indicate that epidermal growth factor (EGF) is a potent mitogen to normal pituitary cells. Its receptor (EGFR or c-erbB-1), a cellular homologue of a viral oncoprotein erbB, is knonw to be overexpressed in many tumors, but little is known about the expression of EGF and EGFR in pituitary tumors. Immunocytochemical analyses of EGF, EGFR, and c-erbB-2 (an EGFR-related oncoprotein) were carried out on paraffin-embedded sections of 54 pituitary tumors. In sections from normal pituitary, EGF was localized mainly in the gonadotrophs and thyrotrophs. EGFR was detected in only 5-10% of the cells in all of the normal pituitary sections and was almost undetectable in all (34/34) of the hormone-secreting tumors (19 GH-, 9 ACTH-, 4 PRL- and 2 TSH-secreting tumors). However, in 16/20 of the samples from clinically nonfunctioning tumors, EGFR was markedly overexpressed. The EGFR found in these tumors and in the normal tissue was not the truncated form of the EGFR because all sections stained positively with monoclonal antisera to both the intra- and extracellular domains of the EGFR. EGF was coexpressed in the same NFT samples that stained positively for EGFR and was also found in 2/19 GH-, 2/4 PRL-, and 1/2 of TSH-secreting tumors. The expression of c-erbB-2 was detected in all normal tissue, all NFT, and about half of GH-secreting tumors. No correlation was found with clinical parameters other than tumor categories. Because the overexpression of structurally intact EGFR was confined to NFT, the response of the tumor cells to EGF in vitro was examined. The addition of 1 nM EGF to NFT-derived cells resulted in an increase in [3H]thymidine uptake to 237.5 +/- 19.8% (mean +/- SEM, n = 3) of the control value. EGF also stimulated EGFR messenger RNA levels, shown by Northern blot analysis. In contrast, the expression of glycoprotein hormone common alpha-subunit gene in the tumor cells was reduced by EGF, T3, and 17 beta-estradiol. The novel findings of overexpression of EGFR in most NFT combined with the in vitro response to EGF resulting in an increase in tumor cell growth, up-regulation of EGFR gene and suppression of hormone gene expression implicate a role for EGF and its receptor in the development and/or progression of NFT.
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PMID:Expression of epidermal growth factor (EGF), its receptor, and related oncoprotein (erbB-2) in human pituitary tumors and response to EGF in vitro. 795 24

It is not clear which growth factors are crucial for the survival, proliferation, and differentiation of pancreatic beta-cells. We used the relatively differentiated rat insulinoma cell line INS-1 to elucidate this issue. Responsiveness of the DNA synthesis of serum-starved cells was studied to a wide variety of growth factors. The most potent stimulators were PRL, GH, and betacellulin, a member of the epidermal growth factor (EGF) family that has not previously been shown to be mitogenic for beta-cells. In addition to these, only vascular endothelial growth factor, insulin-like growth factor-1 and -2, had significant mitogenic activity, whereas hepatocyte growth factor, nerve growth factor-beta, platelet-derived growth factors, basic fibroblast growth factor, EGF, transforming growth factor-alpha (TGF-alpha), neu differentiation factor, and TGF-beta were inactive. None of these factors affected the insulin content of INS-1 cells. In contrast, certain differentiation factors, including nicotinamide, sodium butyrate, activin A, and 1,25-dihydroxyvitamin D3 inhibited the DNA synthesis and increased the insulin content. Also all-trans-retinoic acid had an inhibitory effect on cell DNA synthesis but no effect on insulin content. From these findings betacellulin emerges as a novel growth factor for the beta-cell. Half-maximal stimulation of INS-1 DNA synthesis was obtained with 25 pM betacellulin. Interestingly, betacellulin had no effect on RINm5F cells, whereas both EGF and TGF-alpha were slightly mitogenic. These effects may possibly be explained by differential expression of the erbB receptor tyrosine kinases. In RINm5F cells a spectrum of erbB gene expression was detected (EGF receptor/erbB-1, erbB-2/neu, and erbB-3), whereas INS-1 cells showed only expression of EGF receptor. Expression of the erbB-4 gene was undetectable in these cell lines. In summary, our results suggest that the INS-1 cell line is a suitable model for the study of beta-cell growth and differentiation because the responses to previously identified beta-cell mitogens were essentially similar to those reported in primary cells. In addition, we have identified betacellulin as a possible modulator of beta-cell growth.
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PMID:Growth factor-mediated proliferation and differentiation of insulin-producing INS-1 and RINm5F cells: identification of betacellulin as a novel beta-cell mitogen. 952 26

Treatment of HC11 mammary epithelial cells with the lactogenic hormone PRL promotes differentiation and induction of milk protein gene expression via stimulation of the Janus kinase (JAK)/signal transducer and activator of transcription pathway. We have previously shown that autocrine activation of epidermal growth factor (EGF) receptor interferes with normal PRL-induced differentiation. Here we show that PRL activation of JAK2 was dramatically reduced in HC11 cells pretreated with EGF, demonstrating that the target of EGF receptor activation is JAK2 kinase. Using an in-gel protein tyrosine phosphatase (PTP) assay, we observed that the activity of a 125-kDa PTP was up-regulated in HC11 cells in response to EGF. A specific antiserum was used to demonstrate that the 125-kDa PTP was PTP-PEST and to show that EGF treatment of HC11 cells led to an increase in the level of PTP-PEST. In intact HC11 cells, PTP-PEST was constitutively associated with JAK2, and in response to EGF treatment there was an increased level of PTP-PEST in JAK2 complexes. An in vitro phosphatase assay, using PRL-activated JAK2 as the substrate and lysates from HC11 cells as the source of PTP-PEST, revealed that JAK2 could serve as a PTP-PEST substrate. However, in intact cells the regulation of JAK2 by PTP-PEST was complex, since transient overexpression of PTP-PEST had a negligible effect on PRL-induced JAK2 activation. EGF's negative influence on JAK2 activity was blocked by actinomycin D treatment of HC11 cells, suggesting that EGF induced a protein that mediated the effects of PTP-PEST on JAK2. In support of this model, PTP-PEST-containing lysates from EGF-treated HC11 cells dephosphorylated JAK2 to a greater extent than lysates prepared from control cells.
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PMID:The protein tyrosine phosphatase-PEST is implicated in the negative regulation of epidermal growth factor on PRL signaling in mammary epithelial cells. 1173 19

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration.
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PMID:Evidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway. 1288 91