• Journal of Animal Science and Technology
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• v.44 no.6
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• pp.653-660
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• 2002

We considered KIT gene as a candidate gene for the white-spotting pattern in cattle. This study was carried out to detect genetic variation of c-KIT receptor gene and to investigate association between the mutation and the white-spotting pattern in cattle. PCR-RFLP analysis within intron 6 of c-KIT receptor gene were performed with 8 cattle breeds including Hanwoo, Angus, Brown Swiss, Charolais, Hereford, Holstein, Limousin and Simmental. When PCR product of approximately 2,440 bp including intron 6 of c-KIT receptor gene was sequenced, four nucleotide substitutions were found within intron 6 of the bovine c-KIT receptor gene. In PCR-RFLP analysis, three alleles (A, B and C), two alleles (A and B) and two alleles (A and B) at each locus were identified by MspⅠ, BsrBⅠ and NdeⅠ, respectively. Although frequencies of allele at each locus were different among cattle breeds, we could not get any evidence related with white or white spotting phenotypes in these mutations on intron 6 of c-KIT receptor gene. However, we can not entirely exclude the possibility that c-KIT receptor gene is responsible for white spotting phenotype in cattle. Thus, further studies need to detect other mutations in c-KIT receptor gene and to test association of those mutations and coat color phenotypes in cattle.

• Korean Journal of Clinical Laboratory Science
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• v.37 no.1
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• pp.41-46
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• 2005

It is known that mast cells (MCs) are increased in H. pylori-infected gastritis and its increase is mediated by stem cell factor (c-kit ligand). To determine the mechanism of mast cell recruitment and activation by stem cell factor, weinvestigated the expression of stem cell factor receptor (c-kit) in H. pylori-positive and -negative gastric mucosa. Biopsy specimens from 16 H. pylori-negative and 20 positive subjects were examined. H. pylori infection in gastric mucosa was examined by the Warthin-Starry method. MC and c-kit were identified by immunohistochemisty, using a monoclonal antihuman MC tryptase antibody and a polyclonal anti-human c-kit antibody. Densities of MC and c-kit positive cell were measured by a computerized image analysis system. MCs were detected in the lamina propria of both H. pylori-positive and -negative gastric mucosa. Densities of MC and c-kit positive cell were significantly greater in H. pylori-positive than -negative subjects. c-kit was located on the surface of MCs. These results indicate that stem cell factors may be one of the factors involved in mast cell increase and that they activate mast cells by binding with c-kit.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.2
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• pp.87-95
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• 2022

Receptor tyrosine kinase c-Kit, a marker found on interstitial cells of Cajal (ICCs), is expressed in Leydig cells, which are testicular interstitial cells. The expression of other ICC markers has not yet been reported. In this study, we investigated the expression of c-Kit and anoctamin 1 (ANO1), another ICC marker, in mouse testes. In addition, the relationship between c-Kit and ANO1 expression and Leydig cell function was investigated. We observed that c-Kit and ANO1 were predominantly expressed in mouse Leydig cells. The mRNA and protein of c-Kit and ANO1 were expressed in TM3, a mouse Leydig cell line. LH induced an increase in intracellular Ca²⁺ concentration, membrane depolarization, and testosterone secretion, whereas these signals were inhibited in the presence of c-Kit and ANO1 inhibitors. These results show that c-Kit and ANO1 are expressed in Leydig cells and are involved in testosterone secretion. Our findings suggest that Leydig cells may act as ICCs in testosterone secretion.

• Reproductive and Developmental Biology
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• v.29 no.2
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• pp.109-115
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• 2005

Hematopoietic stem cells (HSC) are multipotent cells that reside in the bone marrow and replenish all adult hematopoietic lineages throughoutthe lifetime. In this study, we analyzed the expression of receptors of $P2Y_{10}$, purinergic receptor families in murine hematopoietic stem cells, hematopoietic progenitor cells. In addition, the biological activity of $P2Y_{10}$ was investigated with B lymphocyte cell line, Ba/F3 in effect to cell growth and cell cycle. From the analysis of expression in hematopoieticstem cell. and progenitor with RT-PCR, $P2Y_{10}$ was strongly expressed in murine hematopoieticstem cells (c-kit+ Sca-l+ Lin-) and progenitor cell population, such as c-kit- Sca-l+ Lin-, c-kit+ Sca-l- Lin- and c-kit- Sca-l- Lin-. To investigate the biological effects by $P2Y_{10}$, retroviral vector from subcloned murine $P2Y_{10}$ cDNA was used fur gene introduction into Ba/F3 cells, and stable transfectant cells were obtained by flow cytometry sorting. In cell proliferation assay, the proliferation ability of $P2Y_{10}$ receptor gene­transfected cells was strongly inhibited, and the cell cycle was arrested at G1 phase. These result suggest that the $P2Y_{10}$ may be involved the biological activity in hematopoietic stem cells and immature B lymphocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.15-20
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• 2013

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

• Molecules and Cells
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• v.41 no.11
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• pp.971-978
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• 2018

The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.

• Korean Journal of Head & Neck Oncology
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• v.19 no.2
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• pp.121-126
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• 2003

Objectives: The c-kit gene encodes a transmembrane receptor-type tyrosine kinase, which is known to have a significant role in the normal migration and development of germ cells and melanocytes. In the previous studies of c-kit gene, c-kit expressions showed only in adenoid cystic carcinomas, lymphoepithelioma-like carcinomas and myoepithelial carcinomas, but not in others and mutation was not found in any types of salivary carcinoma. We investigate the c-kit expression which may be useful to differentiating adenoid cystic carcinomas from others, and mutation of the gene which may not be exist nor the mechanism of c-kit activation in salivary carcinomas. Material and Methods: The archival tissue samples from 42 salivary carcinomas of major and minor salivary glands were studied for c-kit expression by immunohistochemistry and gene mutation by polymerase chain reaction amplification and single strand conformational polymorphism. Results: The c-kit expressions were noted in 22/24 adenoid cystic carcinomas, 7/9 mucoepidermoid carcinomas, 2/3 acinic cell carcinomas, 3/4 malignant mixed tumors, and one undifferentiated carcinoma. The mutation of c-kit gene was found in 3/24 adenoid cystic carcinomas, 3/8 mucoepidermoid carcinomas, one acinic cell carcinoma, and 2/4 malignant mixed tumors. Conclusion: c-kit protein overexpression is seen in a variety of salivary gland carcinomas, and the mutation of the gene may be the mechanism of c-kit activation in these neoplasms.

• Journal of Veterinary Clinics
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• v.36 no.6
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• pp.319-324
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• 2019

Receptor tyrosine kinases (RTK) are major promising targets in anticancer therapy in human and veterinary medicine. Using immunohistochemistry method, we evaluated the expressionof five types RTK (PDGFR-α, PDGFR-β, VEGFR 2, c-Kit and Abl) in the six canine brain tumor samples (2 meningioma, 2 astrocytoma, 1 ependymoma and 1 choroid plexus papilloma). A total of five samples expressed PDGFR-β (5/6), one sample, the choroid plexus papilloma, expressed c-Kit (1/6), and a total of two samples expressed Abl (2/6). None of the samples showed expression of PDGFR-α and VEGFR 2. We demonstrate that a significant portion of canine brain tumors express tyrosine receptors for growth factors and show that these receptors generally localize to tumor cell membranes and the cytoplasm. Evaluation of immunohistochemical expression for the RTKs PDGFR-β, c-Kit, and Alb in canine brain samples reveals an interesting potential for molecular targeting by TKIs in therapeutic studies of canine brain tumors, and more studies will be needed to assess the interactions and efficacy of these RTKs and TKIs. Based on these results, we have some evidence for novel chemotherapeutic trials using TKIs for canine nervous tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1495-1499
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• 2015

Background: c-Kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker for demonstrating thrombocyte function. We aimed to investigate whether c-kit is expressed in benign, preneoplastic and neoplastic endometrial tissues and whether MPV has a relation with c-kit expression and its intensity. Materials and Methods: c-Kit expression was investigated immunohistochemically in 10 samples of normal endometrium (n=10), simple endometrial hyperplasia (5 cases with atypia and 10 cases without atypia), complex endometrial hyperplasia (10 cases with atypia and 10 cases without atypia) and endometrial cancer (EC) (10 cases grade I and 10 cases grade II) and MPV of all cases was checked. Results: c-Kit expression was observed at very low rates in cases with normal endometrial tissues (NE) and in hyperplasia without atypia. c-Kit expression and immunostaining were strong in endometrial atypia and EC. MPV levels of complex atypical endometrial hyperplasia (CAEH) (p:0.002), EC grade I (ECG I) (p<0.001) and EC grade II (ECG II) (p<0.001) were significantly elevated when compared with the NE group. Both c-kit expression and intensity of immunostaining had a positive correlation with MPV level. Conclusions: While c-kit expression and intensity of immunostaining were mildly positive in NE and hyperplasia without atypia, they were clearly observed in EC and hyperplasia with atypia. As c-kit expression is related to the mutagenesis a long-term followup may be needed in these cases. A high MPV level may be a good test for demonstrating c-kit expression and intensity of immunostaining.

• BMB Reports
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• v.51 no.8
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• pp.418-423
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• 2018

Emergency granulopoiesis is a very important strategy to supply efficient neutrophil number in response to infection. However, molecular mechanism involved in this process remains unclear. Here, we found that administration of WKYMVm, an immune modulating peptide, to septic mice strongly increased neutrophil number through augmented emergency granulopoiesis. WKYMVm-induced emergency granulopoiesis was blocked not only by a formyl peptide receptor 2 (FPR2) antagonist (WRW4), but also by FPR2 deficiency. As progenitors of neutrophils, $Lin^-c-kit^+Sca-1^-$ cells expressed FPR2. WKYMVm-induced emergency granulopoiesis was also blocked by a phospholipase C inhibitor (U-73122). These results suggest that WKYMVm can stimulate emergency granulopoiesis via FPR2 and phospholipase C enzymatic activity.