Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined a panel of 25 small cell lung cancer (SCLC) cell lines and nude mouse xenografts for expression of the proto-oncogenes c-met and c-kit, and for expression of the corresponding ligands, hepatocyte growth factor (HGF) (also known as scatter factor (SF)), and stem cell factor (SCF), respectively. Expression of mRNA was detected by Northern blotting, and c-met and c-kit protein expression was detected by Western blotting and immunocytochemistry. c-met and c-kit mRNA was expressed in 22 of the examined cell lines or xenografts, and coexpression of the two proto-oncogenes was observed in 20 tumours. Expression of c-met and c-kit protein paralleled in the mRNA expression. HGF/SF mRNA was expressed in two of the examined tumours, and only one of these also expressed the c-met proto-oncogene. SCF mRNA was expressed in 19 of the examined tumours, and in 18 of these coexpression of c-kit and SCF was present. The high percentage of SCLC tumours expressing c-met and c-kit indicates that these proto-oncogenes may have an important function in this disease. The rare coexpression of c-met and HGF/SF is evidence that an autocrine regulatory pathway is not present for this receptor/ligand system in SCLC, while the frequent coexpression of c-kit and SCF indicates that this receptor/ligand system may have an autocrine function in SCLC.
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PMID:Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts. 767 80

Activation of distinct receptor tyrosine kinases (RTK), such as the products of the c-fms and c-kit proto-oncogenes, profoundly affects hematopoietic development. We have isolated a novel RTK cDNA, called met-related kinase (MRK), which is expressed on early erythroid progenitors. MRK is also expressed in many hematopoietic cell lines, and is not lineage restricted. Several regions within the catalytic domain of MRK have amino acid similarity to the c-met proto-oncogene and v-sea oncogene. Specific polyclonal anti-MRK antisera detects an 84-Kd polypeptide in COS cells transfected with an expression vector containing the MRK cDNA. Further studies of this novel RTK will provide potential insight into its role during hematopoiesis.
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PMID:Isolation of a novel receptor tyrosine kinase cDNA expressed by developing erythroid progenitors. 839 55

Previously, we found that hepatocyte growth factor receptor (c-Met)-and alpha-fetoprotein (AFP)-expressing cells were present in adult rat bone marrow, and that these cells also expressed hematopoietic stem cell markers, such as CD34, Thy-1, and c-Kit. When bone marrow cells were cultured in a hepatocyte growth medium (HGM) with HGF and EGF, colonies composed of polygonal cells resembling mature hepatocytes appeared by 2 weeks and grew very slowly because of overgrowth of stromal cells. At days 34-41, 2-mm2 sheets of hepatocyte-like cells were cut out of their colonies by scratching with an injection needle under observation with a phase contrast microscope, transferred into wells of 24-well plates, and cultured in the HGM medium in the presence or absence of HGF and EGF. When cells reached confluence, cells were detached with trypsin and EDTA and transferred step by step into bigger culture vessels. Thus, hepatocyte-like cells were expanded 1000-fold during less than 4 months. These cells were immunocytochemically stained for albumin and also for AFP and the hematopoietic stem cell markers described above, showing characteristics of oval cells. By RT-PCR, we detected mRNAs of tryptophan-2,3-dioxygenase and tyrosine aminotransferase, markers of hepatocytes at a terminal differentiation stage. The present culture system may be useful for supply of hepatocyte resources for cell transplantation therapy.
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PMID:Propagation of adult rat bone marrow-derived hepatocyte-like cells by serial passages in vitro. 1546 80

Pleuro-pulmonary solitary fibrous tumor (SFT) is a relatively uncommon mesenchymal neoplasm of uncertain histogenesis, unknown molecular features, and unpredictable clinical behavior. Although complete resection is universally accepted as the most important single prognostic factor, some clinicopathologic characteristics (gross appearance, tumor size, mitotic index, tumor necrosis, hypercellularity, and pleomorphism) are related to patient outcome, and a staging system based on these parameters with practical therapeutical implications has been recently proposed by de Perrot et al. Here, 88 pleuro-pulmonary SFTs were collected and clinicopathologic characteristics including de Perrot classification, patients' follow-up, p53 expression, and several "targetable" kinases [c-kit, v-raf murine sarcoma viral oncogene homolog B1, platelet-derived growth factor receptor (PDGFR)-alpha/beta, c-met, epidermal growth factor receptor (EGFR)] were retrospectively analyzed. Fifty-two cases (59%) had at least 1 clinicopathologic feature related to malignancy, whereas mortality and recurrences occurred in 10.2% and 18.2% of the cases, respectively. de Perrot staging and high p53 expression were significantly related to the conventional clinicopathologic prognostic features as well as to overall survival (OS) and disease-free survival (DFS) (P<0.001). At multivariate analysis, high p53 expression and tumor necrosis were the only parameters significantly associated with OS and DFS (P=0.017 and P=0.012, respectively). Immunohistochemical expression was frequently detected for PDGFR-alpha (97.7%), PDGFR-beta (86.5%), and hepatocyte growth factor receptor (96.6%), whereas missense mutations were only identified in 2 cases both involving PDGFR-beta (exons 18 and 20). We conclude that de Perrot stratification of SFT is a reliable prognostic indicator and merits consideration in view of its suggestions for the management of these tumors in daily practice. p53 expression may represent a valid and easy-to-test prognostic factor significantly related to OS and DFS. Although mutations of the corresponding genes are rare events in SFT, PDGFR-alpha/beta, and hepatocyte growth factor receptor tyrosine kinases should be further investigated given the availability of specific inhibitory molecules which might provide useful and novel therapeutical approaches for SFT patients.
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PMID:Pleuro-pulmonary solitary fibrous tumors: a clinicopathologic, immunohistochemical, and molecular study of 88 cases confirming the prognostic value of de Perrot staging system and p53 expression, and evaluating the role of c-kit, BRAF, PDGFRs (alpha/beta), c-met, and EGFR. 1875 43