Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparative immunohistochemical study of intermediate filament expression in normal parotid glands and pleomorphic adenomas (PA) was performed using material fixed in a modified methacarn fixative. The normal myoepithelial cells of acini stained only with monoclonal antibodies 312C8-1 (cytokeratin (CK) 14) and 4.62 (CK 19) while myoepithelial/basal cells of ducts also reacted with antibodies 8.12 (CK 13, 16), 8.60 (CK 10, 11, +/- 1), and PKK1 (CK 7, 8, 17, 18). Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60. In PA, tumour cells at the periphery of ducts, in solid areas, and at the edge of myxoid regions all had CK profiles similar to normal myoepithelial/basal cells except that antibody 4.62 was generally negative. Vimentin and glial fibrillary acidic protein (GFAP) were uniformly negative in normal parotids but showed variable (often strong) reactivity with some cells in chondroid, myxoid and solid areas of PA. A surprising feature of most PA was the variability of CK subtype expression not only from one case to another but also within morphologically similar areas of the same specimen. These results suggest that the morphology of PA is the result of diversity of tumour cell differentiation rather than the processes implicit in a reserve cell histogenetic model.
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PMID:Intermediate filament expression in normal parotid glands and pleomorphic adenomas. 245 77

Epithelial differentiation antigens have been correlated with morphologic differentiation of neoplastic urothelium. Moreover, epidermal growth factor, which is a polypeptide regulating growth and differentiation of normal and neoplastic cells, is found in high concentrations in the urine while its receptors (EGFR) have been identified in bladder tumors. The aim of this study was to investigate the immunohistochemical expression of cytokeratin, epithelial membrane antigen (EMA), CEA and EGFR in transitional cell bladder carcinomas (TCC) and to define any correlation of their expression with tumor grade, stage and patient survival. Twenty-four biopsy specimens obtained from patients with TCC were studied retrospectively. There were 23 men and 1 woman with a mean follow-up of 64 months. Eight biopsy specimens, which represented tumor recurrences of 4 patients, were also included in our material. The immunohistochemical avidin-biotin complex method was performed on paraffin sections for the detection of cytokeratin and EGFR with monoclonal antibodies as well as CEA with a polyclonal antibody. Cytokeratin was detected in 83.5% of the TCC, EMA in 62% and CEA in 70%. The expression of the epithelial differentiation antigens in TCCs was heterogenous, showing an increased incidence in high-grade and high-stage TCC. The CEA expression in TCC demonstrated a statistically significant correlation with patient survival (p < 0.02). EGFR was detected in 50% of the TCC. Although not statistically significant, a trend was found for a higher percentage of EGFR detection in high-grade TCC. EGFR expression was significantly associated with tumor stage and patient survival (p < 0.01 and p < 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epithelial differentiation antigens and epidermal growth factor receptors in transitional cell bladder carcinoma: correlation with prognosis. 754 21

Human skin is believed to harbor a reservoir population of precursor melanocytes. It has been difficult to identify these putative cells experimentally, because they lack phenotypic features that define mature melanocytes. We have evaluated expression of the KIT tyrosine kinase receptor, which is critical for melanocyte development, as a possible marker of these cells. Sections of human skin were evaluated with single- and double-immunolabeling techniques. KIT-reactive dendritic cells were identified in the basal layer of the epithelia and were most numerous in the follicular infundibula and the rete ridges. These cells were located on the epithelial side of the basement membrane and lacked expression of cytokeratin and mast cell tryptase. The location of the KIT-reactive cells was distinctly different from that of Langerhans cells (identified with anti-CD1a) or Merkel cells (identified with CAM 5.2). Within the epidermis and upper follicular infundibulum the majority of the KIT-reactive dendritic cells also coexpressed TRP-1, a marker present in differentiated melanocytes. In the deeper follicular regions, the coexpression of TRP-1 in the KIT-reactive cells was absent. Throughout the epidermis and follicle, however, the KIT-reactive cells coexpressed BCL-2, a marker known to be increased in melanocytes. Thus, KIT expression reveals a population of intraepithelial cells that have immunophenotypic characteristics of mature melanocytes within the upper epithelial regions, but lack the differentiated melanocytic phenotype within the deeper follicular regions. We propose that these KIT(+), BCL-2(+), and TRP-1(-) cells constitute a precursor melanocyte reservoir of human skin.
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PMID:KIT expression reveals a population of precursor melanocytes in human skin. 861 59

Keratinocyte growth factor (KGF) is synthesized and secreted exclusively by mesenchymal cells, and acts through its receptor (KGFR) to stimulate epithelial proliferation. In vivo, KGF and KGFR comprise a mesenchymal-epithelial cell paracrine system that can mediate epithelial cell mitosis. In preliminary work, we noted that KGF was expressed in the rhesus monkey placenta, and we now report on the expression of placental KGF and KGFR mRNAs during the course of gestation in this species. In-situ hybridization revealed that during early gestation, KGF mRNA was strongly expressed in placental mesenchymal cells. These cells, which were also immunoreactive for vimentin, were mainly located on the periphery of the mesenchymal cores of both anchoring and floating villi. KGFR mRNA was expressed in the adjacent trophoblastic epithelium, which was immunoreactive for cytokeratin. In-situ hybridization revealed that KGF mRNA expression was very high in the youngest placentae (34-days gestation) and decreased gradually to minimal levels by late gestation (157 days). Northern blot analysis indicated also that the KGF MRNA signal was strongest in early gestation samples and weakest by late gestation. Analysis for KGFR mRNA by a reverse transcriptase-polymerase chain reaction technique showed that KGFR mRNA expression could be detected at all stages. However, in-situ hybridization indicated that KGFR mRNA expression was highest in early gestation placentae and least in the oldest placentae. Autoradiographs of frozen sections of placenta that had been incubated with [125I]KGF to detect receptor binding showed that grain density over the trophoblast was highest in the youngest and least in the oldest placentae. PCNA and Ki-67 expression followed this same temporal trend. We conclude that the KGF/KGFR system may be important in proliferation of the placental trophoblast during early- to mid-pregnancy in rhesus monkeys.
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PMID:Keratinocyte growth factor and its receptor in the rhesus macaque placenta during the course of gestation. 873 Aug 82

A recent trend in cancer control programmes is the development of early detection strategies and chemoprevention of premalignant lesions. The present study evaluates the potential of selected markers in the biological staging of tumor progression in oral mucosa for better management of the disease. The expression patterns of various cytokeratin protein types such as 10/11, 13 & 16, 19, 18, 14 and pancytokeratin, involucrin, ras p21, epidermal growth factor (EGF) and its receptor (EGFR) were assessed immunohistochemically in various stages of tumor progression in oral mucosa. Statistical analyses such as the Kruskal-Wallis one-way ANOVA, Spearman's rank correlation and multiple regression analysis were carried out to see which proteins have a significant association with tumor progression in oral mucosa. Statistical analysis showed that the expression patterns of cytokeratin types 10/11, 14 and 19, involucrin and epidermal growth factor were significantly correlated with tumor progression in oral mucosa in both univariate and multivariate analysis. Thus the biological stage of a lesion can be calculated from the multiple regression equation derived for these proteins, which could be more useful in assessing the stage of tumor progression in oral mucosa than histopathological grading.
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PMID:Potential biological markers for the staging of tumor progression in oral mucosa: a multivariate analysis. 877 6

Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from different stages of cellular differentiation may have different clinical and pathobiological behavior. To test the hypothesis that HCC can be classified into two types based on its phenotypic markers (hepatocellular and biliary differentiation), liver tissues from 290 Chinese patients with HCC were studied. Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen), biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and transforming growth factor-alpha in the tumor tissue were assessed by immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7% and biliary differentiation markers were detected in 29.3% of these tumors. Clinically, no patient with HCC with biliary markers survived for more than 27 weeks compared with a 22.6% survival rate in patients with HCC negative for biliary markers. HCCs positive for the biliary differentiation markers showed features of more aggressive disease in terms of poorer cellular differentiation (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001; proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without biliary markers. HCCs with biliary markers also had a higher level of expression of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs based on its phenotypic (differentiation) markers has both clinical and pathobiological implications.
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PMID:Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. 886 66

We isolated a cDNA clone, Elk-3, that encodes a novel Ets transcription factor from 16-day mouse embryos. The deduced amino acid sequence of the protein was homologous to human ELK-1 and SAP-1. This protein, ELK-1, and SAP-1 shared some unique structural properties such as an Ets DNA-binding site in the amino-terminal region, a serum response factor interacting domain and phosphorylation sites of serine or threonine residues in the carboxy-terminal region. Northern blotting weakly revealed that two transcripts of 4 and 2.1 kb are expressed in the adult ovary and lung and a 2.1-kb transcript predominated in 8- to 14-day embryos. We assayed the transcriptional activities of Elk-3 protein on the cytokeratin EndoA enhancer containing Ets binding sites in endodermal cells. Elk-3 protein strongly repressed enhancer activity but did not affect the activity of the basal promoter in the absence of the enhancer. Furthermore, Elk-3 can suppress the activity of Ets-2 as the transcriptional activator on the EndoA enhancer. These data suggested that the Elk-3 gene product plays a role in transcriptional regulation during embryogenesis.
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PMID:Molecular cloning of Elk-3, a new member of the Ets family expressed during mouse embryogenesis and analysis of its transcriptional repression activity. 889 57

A primary culture system of olfactory cells derived from newborn mouse was established by coculturing with a feeder layer of brain astrocytes. In this system, the whole lifespan of olfactory cells could be observed in vitro. Neurogenesis occurred from 5 days after plating and coexistence of immature and mature olfactory cells was observed until day 14. After day 15, immature cells were diminished and most of the culture cells appeared differentiated after day 20. The lifespan of differentiated cells was estimated to be 3 to 6 weeks. Cultured cells expressed growth associated protein 43 (GAP43), neurofilament protein (NFP), protein gene product 9.5 (PGP9.5) and olfactory marker protein (OMP). In addition, other round cells were cytokeratin-positive by immunostaining. RT-PCR of growth factor receptors on the coculture cells revealed the expressions of fibroblast growth factor receptor 2 (FGFR2) and FGFR3, both of which could not be detected in the feeder cell layer of astrocytes. FGFR1 and transforming growth factor beta receptor (TGF beta R) were detected both on the coculture and on feeder cells. FGFR4, insulin-like growth factor 2 receptor (IGF2R) and hepatocyte growth factor receptor (HGFR) could not be detected in both samples. Furthermore, basic FGF, a prototypic FGF, was also found in the coculture system and in feeder cells. The present study indicated FGF might affect regulation of proliferation and differentiation of olfactory cells.
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PMID:[Proliferation and differentiation of olfactory cells in primary culture system]. 910 46

Interactions between the ureteric bud (UB) and metanephric mesenchyme are crucial for tubulogenesis during kidney development. Two immortalized cell lines derived from the day 11.5 embryonic kidney, UB cells, which appear to be epithelial (cytokeratin-positive, E-cadherin-positive, and ZO-1-positive by immunostaining) and BSN cells, which are largely mesenchymal (vimentin-positive, but negative for cytokeratin, cell surface E-cadherin, and cell surface ZO-1), were used to establish an in vitro tubulogenesis system. BSN cells expressed hepatocyte growth factor (HGF) and transforming growth factor-beta1 mRNAs, and its conditioned medium (BSN-CM) contained factors capable of activating the epidermal growth factor (EGF) receptor (EGFR). When UB cells were cultured in an extracellular matrix gel in the presence of the embryonic kidney or BSN-CM, the UB cells underwent morphogenetic changes characteristic of early in vitro branching tubulogenesis. These changes were largely inhibited by a combination of neutralizing anti-HGF antibodies and the EGFR inhibitor tyrphostin AG1478, suggesting that EGFR ligands, together with HGF, account for much of this early morphogenetic activity. Nevertheless, there was a significant fraction of tubulogenic activity that could not be inhibited, suggesting the existence of other soluble factors. Whereas HGF, EGF, transforming growth factor alpha, basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1), or a mixture of these growth factors, induced epithelial processes for up to 3 days, only IGF-1, possibly bFGF, and the mixture were able to sustain morphogenesis for longer periods, though not nearly to the same degree as BSN-CM. Moreover, only BSN-CM induced branching tubular structures with clear lumens, consistent with the existence of other soluble factors crucial for the formation and/or maintenance of branching tubular structures with lumens in vitro.
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PMID:An in vitro tubulogenesis system using cell lines derived from the embryonic kidney shows dependence on multiple soluble growth factors. 917 8

We examined whether primary cultures of rat retinal pigment epithelial (RPE) cells and RPE cells of an immortalized rat cell line, BPEI-1, would be responsive to the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), which are known to be potent trophic factors for neuronal cells. Primary RPE cell cultures were characterized by indirect immunofluorescence and exhibited positive immunoreactivity for RET-PE2, a monoclonal antibody that recognizes RPE cells, and for the intermediate filaments cytokeratin and vimentin. The survival of cultured RPE cells in serum-free defined medium in the presence of CNTF or LIF was investigated during a 0- to 5-day period. Both CNTF and LIF, at concentrations of 1-50 ng/mL (4-200 pM), markedly enhanced RPE cell survival. Bromodeoxyuridine labelling of RPE cells revealed an increased mitotic activity in cell cultures treated with either CNTF or LIF in comparison to untreated serum-free cultures. Increases in cell survival and proliferation after neurokine treatment were also observed with the BPEI-1 cell line. However, in comparison to the primary RPE cultures, LIF was more effective than CNTF in promoting survival of the cell line over a 5-day treatment period. These studies demonstrate that the neurokines CNTF and LIF are potent trophic factors for mammalian RPE cells in vitro and may serve as candidate therapeutic agents in degenerative conditions that affect the retina and RPE.
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PMID:Mammalian retinal pigment epithelial cells in vitro respond to the neurokines ciliary neurotrophic factor and leukemia inhibitory factor. 925 Mar 59


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