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)

We have studied separated normal human breast epithelial and myoepithelial cells for the presence of basic fibroblast growth factor (FGF2) and its receptors, both low (heparan sulfate proteoglycans) and high affinity (FGFR1), and for the effects of FGF2 on the proliferation of both cell types. Our results indicate that these cells differ markedly in their synthesis and response to FGF2. We found, using PCR of purified cell populations, mRNA for FGF2 only in the myoepithelial cells, whereas immunostaining and Western blotting results demonstrated the presence of FGF2 protein in both epithelial and myoepithelial cells. FGF2 had no effect on the proliferation of myoepithelial cells, but it did maintain the survival of the separated epithelial cells in low serum and stimulate their growth in 5% and 10% FCS. Immunostainable FGFR1 was present in epithelial cells and, to a lesser extent, in myoepithelial cells. Low-affinity binding sites for FGF2 were synthesized by epithelial and myoepithelial cells, but myoepithelial cells possessed a greater proportion of higher-affinity heparan sulfate proteoglycans. These results indicate that myoepithelial cell-derived FGF2 may be an important paracrine factor controlling epithelial cell survival and growth in the normal human breast.
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PMID:A paracrine role for myoepithelial cell-derived FGF2 in the normal human breast. 922 82

We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross-hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed in the rostral presomitic mesoderm, but down-regulated immediately after the formation of the segmented somites. To determine the function of MesP2 protein (MesP2) in somitogenesis, we generated Mesp2-deficient mice by gene targeting. The homozygous Mesp2 (-/-) mice died shortly after birth and had fused vertebral columns and dorsal root ganglia, with impaired sclerotomal polarity. The earliest defect in the homozygous embryos was a lack of segmented somites. Their disruption of the metameric features, altered expression of Mox-1, Pax-1, and Dll1, and lack of expression of Notch1, Notch2, and FGFR1 suggested that MesP2 controls sclerotomal polarity by regulating the signaling systems mediated by notch-delta and FGF, which are essential for segmentation.
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PMID:Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. 924 90

Fibroblast growth factor 2 (FGF2), also known as basic fibroblast growth factor (bFGF), belongs to the FGF family, which consists of at least 9 closely related members. FGF2 is a potent mitogen for fibroblasts derived from normal prostate and, to a lesser extent, for prostatic epithelial cells. Its role in the physiology of the normal prostate seems to be limited to stromal cells, whereas in prostate cancer FGF2 may also have an autocrine/paracrine effect on epithelial cells. In order to better understand the effects of FGF2 on the prostatic epithelium, especially its role in the progression of prostate cancer by establishing an autocrine-stimulation loop, we transfected FGF2 cDNA into a human prostatic epithelial cell line, PNT1A, immortalized with SV40 large-T antigen. This cell line is non-tumorigenic and expresses a high-affinity FGF2 receptor, FGFR1/flg. We characterized 3 independent FGF2-transfected clones and found that the establishment of an FGF2 autocrine loop on these cells led to (i) serum-independent growth, (ii) increased proliferation and (iii) anchorage-independent growth. Such results argue in favor of the possible action of FGF2 on progression of prostate cancer via an FGF2 autocrine loop on epithelial cells.
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PMID:Constitutive expression of FGF2/bFGF in non-tumorigenic human prostatic epithelial cells results in the acquisition of a partial neoplastic phenotype. 924 2

Several mutations involving the fibroblast growth factor receptor (FGFR) gene family have been identified in association with phenotypically distinct forms of craniosynostosis. One such point mutation, resulting in the substitution of proline by arginine in a critical region of the linker region between the first and second immunoglobulin-like domains, is associated with highly specific phenotypic consequences in that mutation at this point in FGFR1 results in Pfeiffer syndrome and analogous mutation in FGFR2 results in Apert syndrome. We now show that a much more variable clinical presentation accompanies analogous mutation in the FGFR3 gene. Specifically, mental retardation, apparently unrelated to the management of the craniosynostosis, appears to be a variable clinical consequence of this FGFR3 mutation.
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PMID:Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis. 927 53

Numerous in vitro studies indicate that fibroblast growth factors (FGFs) play a role in both the development and maintenance of oligodendrocytes. Addition of FGF to mature oligodendrocytes in culture was reported to downregulate the expression of genes encoding proteins of the myelin sheath and to induce a loss of myelin compaction. In this study, a model was developed to functionally block FGF signaling in oligodendrocytes in vivo, by generating transgenic mice expressing a dominant-negative FGF receptor (FGFR1), under the control of the myelin basic protein (MBP) promoter. To demonstrate the effectiveness of this model, truncated FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was confirmed that FGF-signalling was blocked in these cells. Subsequently, five independent transgenic lines ("MBP-FRD") were generated. Three lines expressing the highest level of the transgene were further studied. Initial investigation by Western blot and light microscopic analyses revealed no apparent alterations in myelination of the MBP-FRD mouse brains. However, ultrastructural analysis of myelinated optic nerve fibres from two independent MBP-FRD lines revealed a significant increase in myelin thickness as a function of fibre diameter for both transgenic lines (13% and 16% increase). This increase in myelin thickness was not accompanied by alterations in myelin compaction. These results support the idea that FGF signaling in oligodendrocytes plays a role in the modulation of axon myelination in vivo.
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PMID:FGF plays a subtle role in oligodendrocyte maintenance in vivo. 928 17

Cellular interactions between stroma and epithelium are important in the growth and proliferation of prostate cancer. Peptide growth factors may facilitate the progression of prostate cancer as autocrine and/or paracrine factors. Keratinocyte Growth Factor (KGF or FGF7) has a differentiative and proliferative effect on the epithelium of the developing rat prostate. We investigated if KGF may act as a paracrine agent in human prostate cancer and examined the expression of KGF and Fibroblast Growth Factor Receptors (FGFRs) (IIIb and IIIc isoforms of the FGFR1 and FGFR2 genes). Sixty-five percent (11 out of 17 informative cases) of prostate cancers (CaP) expressed KGF mRNA by RT-PCR, while KGF expression was not detected in benign prostatic hyperplasia (BPH) (n = 6). Upregulation of KGF expression was related to hormone insensitive tumours (P<0.05). Tumour grade and stage were not associated with KGF expression. The source of KGF expression was further characterised using an in vitro primary culture model, showing its restriction to the prostatic stroma. The FGFR1IIIb isoform was expressed in all cases of prostate cancer (n = 17), and FGFR1IIIc mRNA was not detected. In the BPH group, FGFR1IIIb transcripts were detected in four out of six cases. FGFR2IIIb expression was detected in five of six cases of BPH and twelve out of seventeen (71%) cases of prostate cancer. In CaP, though not reaching statistical significance, the persistence of FGFR2IIIb expression appeared to be associated with hormone insensitive tumours (P=0.052). FGFR2IIIc expression was present in eleven of seventeen tumours but was absent in all six cases of BPH. Functional assessment of recombinant KGF in a proliferation assay demonstrated a mitogenic effect of up to 100% on cultured prostatic epithelial cells.
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PMID:Keratinocyte growth factor expression in hormone insensitive prostate cancer. 928 67

Fibroblast growth factors may play an important role in the differential growth of the skull, brain, and facial prominences. In order to understand the role of FGFs in vivo, we have analyzed the competency of head mesenchyme to respond to FGFs via expression of the high affinity receptors FGFR1, 2, and 3. Receptor transcripts, especially those of FGFR2 and FGFR3, were localized to specific regions of the head. We raise the possibilities of particular receptor-ligand combinations and the possible functions of these interactions in the morphogenesis of the head, face, and brain. Finally, we discuss the relationship between FGF receptor expression in the chicken and the phenotypes of FGF receptor mutations in humans.
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PMID:Expression of fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3) in the developing head and face. 928 94

Basic fibroblast growth factor (FGF-2) is one of the mitogens that facilitate epithelial proliferation and angiogenesis. We analysed the expression of FGF-2 and type I fibroblast growth factor receptor (FGFR1) in 20 selected cases of human pancreatic carcinoma (PC) in connection with proliferation of tumour cells and intratumour endothelial cells (ECs), using immunohistochemistry and in situ hybridization (ISH). By FGF-2 immunostaining, tumour cells were strongly positive in 10 cases (50%). By FGFR1 immunostaining, stromal fibroblasts and ECs occasionally showed positive staining. Tumour cells in 12 cases (60%) were strongly positive. Expression of FGF-2 mRNA, as examined by ISH, was detected in 12 cases (60%) of PC, and its distribution pattern was similar to that of FGF-2 immunostaining. We divided these cases into two groups according to the result of FGF-2 immunostaining, and examined the Ki67 labelling indices of tumour cells and ECs between these two groups. These two proliferative indices were significantly higher in FGF-2-positive than in FGF-2-negative cases (P<0.05, P<0.05, respectively). These findings suggest that the expression of FGF-2 in PC is strongly associated with the proliferation of tumour cells and ECs and its increased expression may give tumour a growth advantage.
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PMID:Expression of basic fibroblast growth factor (FGF-2)-associated with tumour proliferation in human pancreatic carcinoma. 929 90

Basic fibroblast growth factor (bFGF) is a regulator of angiogenesis which is overexpressed in leiomyomas compared with matched myometrium. To understand the physiological significance of this finding we characterized the expression of the type 1 receptor for this ligand (FGFR1). Utilizing reverse transcription-polymerase chain reaction (RT-PCR) we identified the complete and alternatively spliced transmembrane forms and two secreted forms of the FGFR1 in endometrium, myometrium and leiomyomas from all patients. This is the first report of secreted forms in uterine tissue. Proteins consistent with each of these isoforms were identified by Western blot analysis in all three tissues. Immunohistochemistry revealed menstrual cycle-specific regulation of FGFR1 protein in the endometrial stroma of normal women but not in women with leiomyomas and abnormal uterine bleeding. Stromal FGFR1 expression is suppressed in the early luteal phase in normal women, but not in women with leiomyoma-related bleeding. These findings support the role of the bFGF ligand-receptor system in the pathogenesis of leiomyoma-related bleeding and may have implications for fertility and contraception since the differential FGFR1 expression occurs in the peri-implantation period of the early luteal phase.
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PMID:Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding. 929 52

Enlargement of the skull vault occurs by appositional growth at the fibrous joints between the bones, termed cranial sutures. Relatively little is known about the developmental biology of this process, but genetically determined disorders of premature cranial suture fusion (craniosynostosis) provide one route to the identification of some of the key molecules involved. Mutations of the MSX2, FGFR1, FGFR2, FGFR3 and TWIST genes yield new insights, both into normal and abnormal cranial suture biogenesis and into problems of broad interest, such as the conservation of molecular pathways in development, and mechanisms of mutation and dominance.
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PMID:Craniosynostosis: genes and mechanisms. 930 Jun 56


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