Expression of functional c-kit receptors rescues the genetic defect of W mutant mast cells.

Alexander, Warren S.; Lyman, S D; Wagner, Ernst

doi:10.1002/j.1460-2075.1991.tb04936.x

Cited by 34 publications

(28 citation statements)

References 53 publications

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“…Molecular weight markers were run in parallel (not shown). The sizes of Kit transcripts detected were consistent with those expected for endogenous (5.5 kb) and viral (6 and 6.5 kb) origins (see Alexander et al 1991). Key: Sto, STO murine fibroblasts (negative control); þ , melan-a (þ/þ) melanocytes; rs, melan-rs cells; 0, not infected; K, infected with LTRkit; L, infected with the LXSN vector only.…”

Section: Non-complementation But Different Effects Of Overexpression supporting

confidence: 78%

“…This vector allows the expression of biologically active Kit receptors in W mutant mast cells (Alexander et al 1991). Murine melanocyte lines melan-rs (rs/rs) and melan-a (wild-type, þ/þ) were infected with the LTRkit and control LXSN viruses (Experimental procedures).…”

Section: Non-complementation But Different Effects Of Overexpression mentioning

confidence: 99%

“…The packaging cell line for retroviruses LXSN and LTRkit was GPþE-86 fibroblasts (Alexander et al 1991); these were grown in Dulbecco's modification of Eagle's medium (DMEM) with 5% FCS, G418 (geneticin) (0.8 mM) and 2-mercaptoethanol (50 M). STO murine fibroblasts were obtained from Dr P.J.…”

Section: Cell Culturementioning

confidence: 99%

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recessive spotting: a linked locus that interacts with W/Kit but is not allelic

et al. 1998

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Background: The murine coat-colour mutation recessive spotting (rs) maps very closely to the W/Kit locus, encoding the proto-oncoprotein Kit, the protein tyrosine kinase receptor for stem cell factor. Kit is important in the development of melanocytes, germ cells, interstitial cells of Cajal (ICC) and haemopoietic lineages, including mast cells. rs has never been genetically separated from Kit, and interacts with Kit mutations, suggesting that it is a recessive allele of Kit. Here we have tested this possibility. We have shown previously that diploid rs/rs melanocytes proliferated more slowly than did þ/þ melanocytes, as did an immortal line of rs/rs melanocytes, melan-rs.

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Section: Non-complementation But Different Effects Of Overexpression supporting

confidence: 78%

Section: Non-complementation But Different Effects Of Overexpression mentioning

confidence: 99%

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recessive spotting: a linked locus that interacts with W/Kit but is not allelic

et al. 1998

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“…Truncation and mutation of feline or murine c-Kit (Besmer et al, 1986;Herbst et al, 1995a), or point mutation of human c-KIT (Furitsu et al, 1993) results in transformation and tumorigenicity. Ectopic expression of normal KIT can also contribute to tumorigenicity: expression of murine or human c-KIT in immortalized ®broblasts such as NIH3T3 cells leads to transformation which is partly factor independent (Alexander et al, 1991;Caruana et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts

1999

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“…With the cloning of SLF it was shown that the full length murine c-Kit could also induce ligand-dependent transformation (Alexander et al, 1991). Neither of these studies investigated the e ect of receptor density on the induction and ligand dependence of transformation.…”

Section: Introductionmentioning

confidence: 99%

Transformation of NIH3T3 fibroblasts by the c-Kit receptor tyrosine kinase: effect of receptor density and ligand-requirement

et al. 1998

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Ectopic expression of the normal murine receptor tyrosine kinase, c-Kit, in NIH3T3 cells induced many phenotypic changes characteristic of transformation including anchorage-independent growth, focus formation and tumorigenicity in nude mice. Although transformation was largely dependent on the presence of recombinant murine Steel Factor (SLF), the ligand to the c-Kit receptor, anchorage independent growth did occur at a low frequency in the absence of added factor, and this could not be inhibited by neutralising antibodies or by SLF anti-sense mRNA. Clones from factor-independent colonies in semi-solid agar displayed a narrow range of c-Kit surface protein levels (4.3 ± 6.4610 4 receptors/cell) which was relatively high compared with the pool from which they were derived. Analysis of a larger series of random clones derived from adherent cultures expressing di erent levels of c-Kit demonstrated a positive correlation between SLF-dependent, anchorage-independent growth and c-Kit protein and mRNA expression levels (respectively, R S =0.58, P50.01; and R S =0.53, P50.01) with consistent colony formation observed with clones having 42.5610 4 receptors/cell. Interestingly, two of the three clones expressing the highest levels of cKit protein and mRNA produced few or no colonies in the presence or absence of SLF. Sequential overexpression of human c-KIT in NIH3T3 cells using a dihydrofolate reductase (DHFR)-encoding vector and gene co-ampli®cation through methotrexate selection, which resulted in pools expressing up to 1.5610 5 receptors/cell, con®rmed that high receptor densities resulted in a decrease in colony numbers. Thus, analysis of clonal and selected populations has indicated that an optimal level of c-Kit is required for transformation of NIH3T3 cells in the presence of SLF, and that some ligand-independent transformation occurs.

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Expression of functional c-kit receptors rescues the genetic defect of W mutant mast cells.

Cited by 34 publications

References 53 publications

recessive spotting: a linked locus that interacts with W/Kit but is not allelic

recessive spotting: a linked locus that interacts with W/Kit but is not allelic

Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts

Transformation of NIH3T3 fibroblasts by the c-Kit receptor tyrosine kinase: effect of receptor density and ligand-requirement

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