Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proto-oncogene c-met product (c-MET) is a receptor tyrosine kinase and functions as a receptor for hepatocyte growth factor (HGF). Although the function of c-MET has yet to be fully clarified, HGF stimulates the phosphorylation of tyrosyl residues on c-MET and triggers the signal transduction pathways, resulting in a contribution to the malignant progression of melanonocytes with synergic factors such as basic fibroblast growth factor and mast cell growth factor. Using immunohistochemical methods, we have studied the localization of c-MET in normal skin and various melanocytic tumours. c-MET was detected in keratinocytes, melanocytes, sebaceous cells, and other cells of the skin. In particular, basal melanocytes almost always showed nuclear labelling. Melanocytic naevi generally revealed predominantly nuclear staining of cells in the epidermis, whereas only a few cases showed a distinct cytoplasmic localization of c-MET in dermal naevus cells. The distribution pattern of c-MET in melanoma cells was basically similar to that of benign lesions, although the numbers tested were small. Cultured human melanoma cells also showed predominantly nuclear labelling, but were unresponsive to exogenous c-MET ligand HGF. Treatment with the glucosidase inhibitor castanospermine caused accumulation of protein at 220 kD, without diminishing the amount of normally-processed 190-kD c-MET. Although there was no significant difference in c-MET distribution between benign and malignant melanocytic lesions, it is suggested that malignant transformation of melanocytes may be associated with loss of response to HGF or other growth-regulating factors.
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PMID:Detection of the c-met proto-oncogene product in normal skin and tumours of melanocytic origin. 782 52

The molecular events responsible for tumor progression in human cutaneous malignant melanoma remain unclear; however, critical to the process is the dysregulated proliferation of tumor cells and the development of new vascular channels which allow further growth and dissemination. Connective tissue mast cells (MC) have been implicated in tumor progression because they concentrate around tumors (including melanomas) prior to the formation of new blood vessels, and because they contain many chemical mediators, including basic fibroblast growth factor (bFGF), known to have mitogenic and angiogenic effects. Several MC chemotactic and mitogenic factors have been described including interleukin-3 (IL-3). In order to determine whether there is a differential expression of this MC chemotactic/mitogenic factor with tumor progression in vivo, we evaluated by immunohistochemistry 85 melanocytic lesions including primary invasive malignant melanoma (PIMM), melanoma in situ (MMIS), and ordinary intradermal benign melanocytic nevi (BMN) for expression of IL-3. Nucleic acid in situ hybridization also was used to evaluate the melanocytic lesions for IL-3-specific mRNA transcripts. Intracellular IL-3 protein was detected in 29/33 (88%) PIMM and 15/25 (60%) MMIS, but was not detected in any (0/27; 0%) BMN (p < 0.0001). IL-3-specific mRNA transcripts were present in 3/4 PIMM and 2/10 MMIS in which IL-3 protein was not identified, but were not detected in any BMN. IL-3 mRNA or protein was not detected in normal melanocytes present in the perilesional epidermis of any of the specimens studied. Immunohistochemistry also was used to confirm the presence of IL-3 alpha-specific receptors on human cutaneous MC. As demonstrated by others, a significantly increased number of MC was present in the perilesional stroma of PIMM and MMIS vis a vis BMN (p < 0.0001). The results suggest that melanoma cells may attract MC in vivo by producing MC chemotactic/mitogenic factors such as IL-3. The recruitment of MC and the subsequent release of their potent mitogenic and angiogenic factors such as bFGF may thus represent a tumor-host interaction which favors tumor progression. Reed JA, McNutt NS, Bogdany JK, Albino AP. Expression of the mast cell growth factor interleukin-3 in melanocytic lesions correlates with an increased number of mast cells in the perilesional stroma: implications for melanoma progression.
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PMID:Expression of the mast cell growth factor interleukin-3 in melanocytic lesions correlates with an increased number of mast cells in the perilesional stroma: implications for melanoma progression. 900 79

A unique combined mastocytoma-junctional nevus presented as a 4-mm dark brown macule in the axilla of a 57-year-old white female. Histopathologic examination revealed a proliferation of mast cells partially or completely filling the dermal papillae, hyperpigmentation of the basal keratinocytes and mildly increased basal melanocytes. Overlying the mast cell proliferation, pigmented junctional nevus nests were present. The mast cells were strongly positive with Giemsa stain and mast cell tryptase immunohistochemical stain; nevomelanocytic cells were negative. Nevomelanocytes were strongly immunoreactive for S100, HMB-45, Mart-1, and tyrosinase; mast cells were negative. The clinicopathologic features suggested a synchronous proliferation of 2 cell types in the same small cutaneous field rather than a collision tumor. While the cutaneous mast cells probably originated as a disseminated clone, it is postulated that local mast cell growth factor induced nevomelanocytic proliferation and modulated mast cell growth. In fact, the tumor exhibited strong immunoreactivity for the mast cell growth factor receptor (CD117) in mast cells, basal melanocytes, and nevus nests. The incidence of dual mast cell-melanocytic tumors appears to be very low, as only 3 total cases have now been reported. However, since in patients with multiple mastocytomas only a small fraction of lesions are biopsied, the true incidence may be higher than supposed.
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PMID:Combined mastocytoma-junctional nevus. 1561 30