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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications.
Cancer Res 1992 Jun 15
PMID:Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene. 137 70

Mutations at the white spotting (w) locus in mice have deleterious effects on germ cells, melanocytes and hematopoietic stem cells. The w locus encodes the c-kit tyrosine-kinase receptor whose ligand is the product of the SI locus. Using monoclonal antibodies (MAb(s)) to the extracellular domain, we have evaluated the expression of c-kit in normal and transformed melanocytes. This cell lineage synthesizes a receptor with a mw of 145 kDa. The gene product is expressed in epidermal melanocytes and in a fraction of nevocytic and blue nevi. In primary melanomas, loss of the receptor is observed in more invasive lesions. Only 30% of the metastatic lesions express detectable levels of the receptor. These findings demonstrate that the c-kit product is down-regulated in melanocytes following malignant transformation. The functional relevance of this modulation remains to be evaluated.
Int J Cancer 1992 Sep 09
PMID:Progression of human cutaneous melanoma is associated with loss of expression of c-kit proto-oncogene receptor. 138 2

Mutations in the Steel locus, encoding a growth factor (Steel factor or SF) or c-kit, the gene encoding its receptor, result in severe anemia in the mouse. In the present study, we have addressed the mechanism of synergistic growth activation, at the cellular level, by SF and GM-CSF using the blast cells of acute myeloblastic leukemia (AML blasts). Our data indicate that SF drastically alleviates the requirement in cell interaction for blast colony formation in most of the samples tested. Analysis of cultures performed in the presence of SF and GM-CSF at different cell concentrations, ranging from 1,000 to 20,000 cells, suggested a single limiting element, i.e., the blast clonogenic cell, while 2 or more limiting elements were found in cultures stimulated with GM-CSF alone, suggesting interacting cell populations. The presence of membrane-bound SF was detected by immunofluorescence, suggesting the possibility that secreted or membrane-bound SF may, at least in part, contribute to the density-dependent growth of AML blasts. In all samples tested, SF appears to increase the responsiveness of AML blasts to GM-CSF, as demonstrated by a 3-fold decrease of GM-CSF half efficient concentration on addition of SF to the cultures. Exposure of AML blasts to SF did not affect GM-CSF receptor expression, suggesting that this increase in GM-CSF responsiveness is likely to occur at the postreceptor level. Interestingly, 2 of 15 AML samples surveyed did not respond to SF, and were both of the myelomonocytic or monocytic subtype, classified as M4 and M5, respectively.
Cancer Res 1992 Oct 01
PMID:Product of the Steel locus can replace leukemic cell interaction. 138 39

The protooncogene c-kit encodes a tyrosine kinase with a molecular weight of 145,000, highly related to the platelet derived growth factor/colony stimulating factor receptors. Mutations of the murine gene result in impairment of hematopoiesis, gametogenesis, and of the melanocyte cell lineage. In order to elucidate c-kit functions in development and oncogenesis we have analyzed immunohistochemically its expression in human normal and transformed nonlymphoid tissues. The receptor has been detected in spermatogonia, melanocytes, and unexpectedly, in astrocytes, renal tubules, parotid cells, thyrocytes, and breast epithelium. While the gene product is expressed in seminoma, lung tumors, and melanoma of low invasiveness, no detectable levels have been detected in thyroid and breast carcinomas, astrocytomas, and invasive melanomas. In breast tumors these findings were confirmed by paired, Northern blot analysis of RNA preparations from normal and transformed tissue. The present results demonstrate that the c-kit receptor plays a role in the development of a larger spectrum of cell lineages. Furthermore, on the basis of the transformation associated changes, we speculate that, while in some cell types, c-kit expression positively regulates mitogenesis and is selected for in neoplastic transformation, in other tissues the c-kit pathway is involved in morphogenesis and differentiation and is, therefore, negatively selected in the course of tumor progression.
Cancer Res 1992 Nov 15
PMID:Expression of c-kit receptor in normal and transformed human nonlymphoid tissues. 138 54

The proto-oncogene c-kit encodes a tyrosine kinase receptor related to the PDGF/CSF-1 receptors. Mutations of this gene result in impairment of hematopoiesis, melanogenesis and gametogenesis. Using monoclonal antibodies to the c-kit gene product, we have analyzed its expression in normal and transformed human tissues. Unexpectedly, the receptor was found to be expressed in normal mammary epithelium. While in benign breast lesions, the c-kit gene product was detected at variable levels in 82% of the instances, in primary tumors, no product could be identified in 87% of the cases. This phenotype is maintained in metastatic foci. These findings were confirmed by paired Northern blot analysis of RNA preparations from normal and tumor tissues. These results demonstrate that the c-kit receptor may also be involved in the growth control of mammary epithelium and that this function may be impaired following malignant transformation and de-differentiation.
Int J Cancer 1992 Nov 11
PMID:Breast cancer is associated with loss of the c-kit oncogene product. 138 36

Mice carrying mutations at the Sl (steel) and W (dominant white spotting) loci develop abnormalities on 3 migratory embryonic stem cell populations: hematopoietic stem cells, neural crest-derived melanocytes, and primordial germ cells. Transplantation experiments have indicated that the Sl locus affects the microenvironment where stem cells migrate, proliferate, and differentiate, while the W locus affects the migratory cells themselves. The Sl locus encodes for a multipotent growth factor known as stem cell factor. The W locus encodes the c-kit protein tyrosine kinase receptor whose ligand is the stem cell factor. We have investigated the incidence and organ distribution of experimental metastases after systemic intra-arterial injection of B16-G3.26 melanoma cells into mutant Sl/Sld and W/Wv mice. Both mutant mouse strains had a markedly lower incidence of ovarian metastases when compared with their congenic +/+ mice. In contrast to the rare colonization of the ovaries, Sl/Sld and W/Wv mice developed metastases in the myocardium, kidney, and stomach--anatomic sites that were infrequently or never affected in their congenic nonmutant mice. The only organs in which the average number of metastatic colonies differed between Sl/Sld and W/Wv mice were the bone marrow and kidneys. The average number of colonized bones per mouse in the Sl/Sld group was 5.0 +/- 3.1 (SD), compared with 12.7 +/- 5.3 in the W/Wv group. The average number of metastatic nodules in the kidneys of Sl/Sld mice was 24.6 +/- 9, while W/Wv mice had 15.5 +/- 2.5. Mutant mice with multiple metastatic nodules in the kidneys, heart, and stomach were also found to have forestomach papillomas, an enlarged duodenum, kidney abnormalities, and small body size. The results of this study provide useful information on potential mechanisms of interaction of metastatic cells with their target organs, and suggest that there are additional organ defects associated with the mutations in the Sl and W loci. They also document the importance of mutant mice in metastasis research.
Cancer Res 1992 Apr 15
PMID:Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). 155 33

Seventy testicular germ cell tumors were analyzed at the DNA and RNA levels for the c-kit, hst-1, and int-2 oncogenes using Northern and Southern blot analyses, respectively. There were significant differences in oncogene expression between seminomas and nonseminomas with c-kit being expressed in 24 of 30 (80%) seminomas but in only 3 of 40 (7%) nonseminomatous tumors (P = 0.0001, chi 2 test) and hst-1 being expressed in 24 of 38 (63%) nonseminomas but only 1 of 24 (4%) of seminomas (P = 0.0001, chi 2 test), demonstrating an inverse relationship in the expression pattern of these 2 oncogenes in human testicular germ cell tumors. A significant association between tumor stage and hst-1 expression in the nonseminoma group was found (P = 0.0002, chi 2 test). No gross alterations in the c-kit, hst-1, and int-2 loci were found at the DNA level and no int-2 mRNA expression was detected in any of the germ cell tumors examined.
Cancer Res 1991 Apr 01
PMID:Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors. 170 18

As an initial step to understand rapid growth of small cell lung cancer (SCLC), a complementary DNA library prepared from a SCLC cell line was screened with viral oncogene probes encoding protein-tyrosine kinases, which are known to play an important role in regulation of cell growth. Fifteen clones hybridizing with v-fms probe were isolated, and, by partial sequence analysis, four of them were identified to be c-kit protooncogenes. Northern blot study demonstrated that most of the SCLC tumors and cell lines expressed c-kit transcripts, while non-SCLC tumors and cell lines did not. Neither amplification nor rearrangement of the c-kit gene was demonstrated in SCLC cell lines by Southern blot analysis, however. Our results suggested that c-kit expression in SCLC reflects the unique biological nature of the tumor cells different from non-SCLC and further suggested that the c-kit product may participate in autocrine or paracrine stimulation of SCLC growth.
Cancer Res 1991 May 01
PMID:Preferential expression of c-kit protooncogene transcripts in small cell lung cancer. 170 53

Stem cell factor (SCF) is a pluripotent growth factor which is suggested to play an important role in proliferation and differentiation in various types of fetal and adult tissues as the ligand of the c-kit proto-oncogene product. However, very little is known about expression of the SCF gene in human malignancies. We analysed DNA and RNA extracted from 28 cell lines and 16 fresh tumor specimens of lung cancer as well as 24 cancer cell lines of various origin for SCF expression. Now we report that the SCF gene is expressed in a wide variety of human cancers including lung cancer, in marked contrast to c-kit, which is expressed in very few types of cancers. As a consequence, coexpression of both the ligand and the receptor is seen only in small-cell lung cancer, suggesting possible involvement of autocrine stimulation via this ligand-receptor system in the pathogenesis of this aggressive cancer. In addition, this study revealed that the human SCF gene is transcribed into two major forms of alternatively spliced mRNAs with different molar ratio in fetal, adult and malignant tissues.
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PMID:Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer. 172 71

Mouse strains carrying mutations at the Dominant White Spotting (W) locus or the Steel (Sl) locus are anemic and display defects in pigmentation and gametogenesis. In W mutants the anemia is due to a deficiency of hemopoietic stem cells and, in Sl mutants, to a deficiency of supporting stromal cells in the bone marrow. The W locus encodes the c-kit proto-oncogene product, a cell surface receptor with protein-tyrosine kinase activity, and the Sl locus encodes its ligand, a hemopoietic cytokine known variously as Steel factor (SLF), mast cell growth factor, stem cell factor, and Kit ligand. SLF can synergize with a number of other cytokines to stimulate growth of hemopoietic progenitors in vitro and stimulates blood cell production in vivo in animals. Here we review the biological activities of SLF, with particular emphasis on its effects on hemopoietic stem and progenitor cells. We also discuss present knowledge of the molecules involved in SLF-triggered signal transduction, and speculate on potential therapeutic applications for SLF in human disease.
Cancer Cells 1991 Dec
PMID:The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. 172 56


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