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

The c-kit proto-oncogene encodes a tyrosine kinase receptor for stem cell factor and plays a critical role in the growth and differentiation of various types of cells including hematopoietic stem cells. To investigate the mechanisms of its transcriptional regulation, we isolated the 5' flanking region of the human c-kit gene and characterized its promoter activity in hematopoietic cells. Nucleotide sequence analysis revealed that the 1.2 kb 5' flanking region lacked a typical "TATA box," but had a relatively high G + C content and four potential Sp1-binding sites. Putative binding sites for AP-2, basic helix-loop-helix proteins, Ets-domain proteins, Myb and GATA-1 were also found. Primer extension and S1 nuclease protection analyses of hematopoietic cells indicated that the major transcription start sites are 62 bp and 58 bp upstream of the translation start site. Essentially the same start sites were detected in non-hematopoietic cells such as small cell lung carcinoma and glioblastoma: this single promoter in c-kit is different from the multiple promoter system of c-fms, a c-kit-related gene, in which at least two promoters are differently used in hematopoietic and non-hematopoietic cells. An analysis of the c-kit 5' flanking region using the bacterial chloramphenicol acetyltransferase gene (CAT assay) in human erythroleukemia HEL cells, which express the endogenous c-kit mRNA at high levels, showed that a region from -180 to -22 is important for the expression of the c-kit gene. In addition, a negative regulatory element(s) is suggested to be involved in the regulation of the c-kit gene expression in mammals.
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PMID:Characterization of the promoter region of the human c-kit proto-oncogene. 750 48

In previous studies, we have characterized the nature and function of the proto-oncogene c-kit, which encodes a receptor tyrosine kinase. This receptor together with its ligand, a stem cell growth factor, constitutes a cell signaling system which is crucial for the development of hematopoietic, melanocytic and germ cells. The expression of the gene correlates with its protein functions in specific cell lineages and is temporally and spatially regulated during fetal and adult life. As a start point to study the gene regulation, we have characterized the promoter of the c-kit gene. A single transcription initiation site located 58 bases upstream of the ATG start codon has been identified. The sequence upstream to the initiation site reveals a TATA-less, non-GC rich promoter. Several potential binding sites for transcription factors pertinent to c-kit expression, such as Sp-1, GATA-1, myb and Oct-4, have been identified. Promoter activities of different lengths of the 5' sequence have been analyzed in transient expression assay. The 2.7 kb of the 5' sequence facilitates the expression of the CAT gene in several cell lines while the sequence further upstream from 2.7 to 5.0 kb shows a negative regulatory activity. This study reveals a unique promoter of the c-kit gene and provides a basis for further elucidation of the regulatory mechanism of c-kit gene expression.
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PMID:Characterization of the promoter of the proto-oncogene c-kit. 753 32

The melanoma cell adhesion molecule was identified as a human melanoma-associated antigen that increases in expression as tumors increase in thickness and begin to acquire metastatic potential. Clinical and experimental evidences suggest that the development of metastatic capacity might be the consequence of increased melanoma cell adhesion molecule expression. The mechanisms for upregulation of the melanoma cell adhesion molecule during melanoma progression are, however, still poorly understood. In this study, we show that melanoma cell adhesion molecule expression is tightly regulated at the transcriptional level. Using a combination of CAT reporter assays and semiquantitative reverse transcriptase-polymerase chain reaction, we observed that cyclic adenosine monophosphate significantly increases transcription of the melanoma cell adhesion molecule in nonmetastatic melanoma cells. In metastatic cells, transcription of the gene was constitutive and could not be further increased by cyclic adenosine monophosphate. On the other hand, melanoma cell adhesion molecule promoter activity was impeded upon treatment with phorbol esters or in the presence of stem cell factor, a phenomenon which was protein kinase C-dependent. Promoter-deletion studies demonstrated that the first 196 nt of the melanoma cell adhesion molecule promoter region are sufficient to get full expression in metastatic melanoma cells. This fragment contains five binding sites for the transcription factor Sp1 and DNA mobility shift experiments showed direct binding of Sp1 to the promoter. In conclusion, our results indicate that Sp1 is sufficient to drive constitutive melanoma cell adhesion molecule expression in metastatic melanoma cells. In nonmetastatic cells, however, melanoma cell adhesion molecule expression is repressed and we speculate that stem cell factor/c-Kit signaling might be responsible for the control of melanoma cell adhesion molecule synthesis, and thus, perhaps, of melanoma progression and metastasis.
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PMID:Regulation of the melanoma cell adhesion molecule gene in melanoma: modulation of mRNA synthesis by cyclic adenosine monophosphate, phorbol ester, and stem cell fFactor/c-kKit signaling. 1057 24

We report a case of gastrointestinal stromal tumor (GIST) with multiple hepatic metastases that responded to tyrosine kinase inhibitor STI571. A 30-year-old woman underwent total gastrectomy on July 10, 1998, with a diagnosis of submucosal tumor of the stomach. Pathological analysis of the primary lesion revealed strong expression of c-kit, and it was diagnosed as GIST. The patient underwent tumor excision due to peritoneal recurrence on May 1, 2000 and November 13, 2000. On August 8, 2001, multiple liver metastases were detected by abdominal CAT scan. Treatment with STI571 at a dose of 400 mg/day for 28 days was initiated on September 14, 2000. CAT scan showed rapid tumor shrinkage after 3 weeks of treatment (reduction rate of 56%) and the response continued after 7 weeks of treatment (reduction rate of 71%). Thus, we evaluated the response as PR. Leukocytopenia, edema, diarrhea and nausea were observed; however, all toxicities were mild and tolerable. This case suggests the efficacy of STI571 for metastatic GIST.
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PMID:[A patient with metastatic gastrointestinal stromal tumor who responded to STI571]. 1197 48

In mice, coat pigmentation requires a stem cell (SC) system in which the survival, proliferation, and differentiation of melanocytes (MCs) are regulated by microenvironments in hair follicles (HFs). In vitro systems are required to analyze the behavior of single melanocyte stem cells (MCSCs) and their potential to form SC systems in vivo. We describe here an experimental system for the isolation, self-renewal, and differentiation of MCSCs, as well as an in vivo reconstitution assay for assessing their potential. Using Dct(tm1(Cre)Bee)/CAG-CAT-GFP mice, we show that, in the presence of stem cell factor and basic fibroblast growth factor and the XB2 feeder cell line, purified MCSCs can undergo clonogenic proliferation, resulting in c-Kit(low) side scatter(low) cells. In culture, these cells maintain their capacity to differentiate and reconstitute an MCSC system in HFs. As these cells are present in the upper part of the HF near the bulge region, express only low levels of housekeeping genes, and are resistant to neonatal treatment with ACK2, it is likely that only MCSCs that are quiescent in vivo have clonogenic activity in vitro. We also found that MCSCs can be purified from wild-type mice by fluorescent cell sorting and can be characterized in vitro.
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PMID:Functional characterization of melanocyte stem cells in hair follicles. 2207 38

A newly found strain, Lactobacillus plantarum CQPC01 (LP-CQPC01), was used for soybean milk fermentation, and its effects against constipation were determined. LP-CQPC01-FSM (LP-CQPC01-fermented soybean milk) was found to have six kinds of soybean isoflavones; the isoflavones of LP-CQPC01-FSM were more than those of Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM). Animal experiment showed that the MTL, Gas, ET, AchE, SP, VIP, and GSH levels in the constipated mice were increased; however, the SS, MPO, NO, and MDA levels in the constipated mice were reduced by soybean milk treatment. Further, LP-CQPC01-FSM increased the mRNA and protein expression of Cu/Zn-SOD, Mn-SOD, CAT, c-Kit, SCF, and GDNF and reduced the expression of TRPV1 and NOS relative to those of the mice with untreated constipation. LP-CQPC01 could be used as a new starter to produce high-quality soybean milk, which might be used as a functional drink.
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PMID:Effects of Lactobacillus plantarum CQPC01-fermented soybean milk on activated carbon-induced constipation through its antioxidant activity in mice. 3128 55