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Query: UNIPROT:P07332 (feline sarcoma)
 360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physiological inducers of myeloid cell growth and differentiation were used to simultaneously analyze the expression of the proto-oncogenes c-myc, c-myb, c-fos, c-fes and c-fms during normal myelopoiesis, where growth is coupled to differentiation, as compared with that in leukemia, where growth has been uncoupled from differentiation as well as upon suppression of the leukemic phenotype via induction of differentiation and growth arrest. Proto-oncogene expression was also used as a tool to dissect the growth to differentiation developmental cascade. Myeloid cell growth was correlated with high c-myc and c-myb RNA levels, decreasing to undetectable levels in terminally differentiated cells. No c-myc RNA was detected in normal myeloid progenitors induced for differentiation without growth, using media conditioned by mouse granulocytes (GCM), indicating that c-myc may play either no role or an inhibitory one in differentiation. RNA levels of the proto-oncogenes c-fos, c-fes and c-fms were undetectable in normal or M1 differentiation inducible (D+) leukemic myeloblasts, and were stably induced upon stimulation of the normal precursors for growth and differentiation, with highest levels at the time when most of the cells had undergone terminal differentiation. Only c-fes RNA was induced upon M1D+ differentiation. It was also shown to be induced upon induction of differentiation without growth in normal myeloid precursors. Using c-myc and c-myb RNA suppression as molecular markers for induction of M1D+ differentiation, the existence of myeloid differentiation factor(s), distinct from myeloid growth factors, has been demonstrated. Such differentiation inducing activity was found in media conditioned by mouse lungs or granulocytes, and was induced in normal myeloid precursors by the myelopoietic growth factors IL3, GM-CSF, G-CSF, and M-CSF. Taken together, the results of this study enhance and add to previous work to better correlate the expression of the proto-oncogenes myc, myb, fes, fos and fms with several parameters of normal and abnormal myeloid cell growth and differentiation. The results indicate that the normal myeloid growth to differentiation developmental cascade entails a mechanism whereby myeloid growth factors induce myeloid differentiation factors, subsequently suppressing c-myc and c-myb RNA expression, leading to the induction of differentiation and growth arrest, including early accumulation of c-fes RNA followed by accumulation of c-fos and c-fms RNAs. It was also indicated that this cascade is impaired in leukemia.
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PMID:Proto-oncogene expression and dissection of the myeloid growth to differentiation developmental cascade. 247 Nov 31

The c-fms protooncogene encodes the receptor for the colony-stimulating factor 1 of macrophages. Its transforming counterpart, the v-fms oncogene has previously been recognized as the transforming gene of the McDonough strain of feline sarcoma virus. We have isolated rabbit antisera against a 115-kDa recombinant polypeptide containing the 926 carboxy-terminal amino acids of the v-fms protein. All antibodies recognized the cytoplasmic domain of the v-fms protein, which is 95% homologous to the corresponding domain of human c-fms proteins. These sera were applied in a survey of various human cancer cell lines, such as peripheral blood mononuclear (HL60) and choriocarcinoma (BeWo) cells, as well as leukemic cells from 58 patients with acute myelocytic, chronic myelocytic or acute lymphocytic leukemias (AML, CML, ALL). Significantly enhanced levels of fms-specific tyrosine kinase activity were detected in 12-O-tetradecanoylphorbol-13-acetate-induced HL60 and in BeWo cells, and in 7 out of 24 samples from AML patients, whereas no activity could be detected in 9 ALL or in 25 CML cell preparations. The AML cells were classified according to the FAB criteria. The highest incidence of increased fms activity was found in cells assigned to the M4 class (four out of five cases). While no activity was found in material belonging to FAB classes M2 or M3, one of the two cases of the M5 class was kinase-positive. Interestingly, two out of seven cases of the M1 class cells exhibited enhanced levels of fms kinase. These data suggest that the determination of the fms kinase may be useful to subdivide the M1 class of the FAB classification into monocytic and non-monocytic precursor leukemia cells.
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PMID:Detection of fms-oncogene-specific tyrosine kinase activity in human leukemia cells. 252 17

The protein encoded by v-fms, the oncogene of the Susan McDonough strain of feline sarcoma virus, is a member of the protein tyrosine kinase family. The kinase activity of the v-fms encoded protein has been reported to be low compared to other members of this enzyme family. We found that the optimal pH in vitro for the autophosphorylation of the immunoprecipitated v-fms encoded protein kinase activity was about pH 5.0; the activity at this pH was 15-fold higher than at the pH (7.4) used in standard kinase assays. The low pH optimum of the kinase activity of the v-fms encoded protein was observed when this protein was immunoprecipitated with each of four independent polyclonal antisera. v-fms proteins from transfected rat, mink or hamster cells all showed the same pH optimum for the kinase activity, as did the protein encoded by the feline c-fms gene. Autophosphorylation of v-fms in vitro at pH 5.0 occurred exclusively on tyrosine residues. Enolase was a substrate for the v-fms encoded protein kinase, and the pH profile for phosphorylation of this substrate in vitro paralleled that seen for the autophosphorylation of v-fms encoded proteins. The discovery of the low pH optimum of the kinase activity exhibited by v-fms proteins may be useful for further characterization of this activity in vitro, as well as for phenotypic classification of other members of the protein tyrosine kinase family.
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PMID:The kinase activity of the v-fms encoded protein has a low pH optimum. 265 15

The Susan McDonough strain of feline sarcoma virus contains an oncogene, v-fms, which is capable of transforming fibroblasts in vitro. The mature protein product of the v-fms gene (gp140fms) is found on the surface of transformed cells; this glycoprotein has external, transmembrane, and cytoplasmic domains. To assess the functional role of these domains in transformation, we constructed a series of nine linker insertion mutations throughout the v-fms gene by using a dodecameric BamHI linker. The biological effects of these mutations on the function and intracellular localization of v-fms-encoded proteins were determined by transfecting the mutated DNA into Rat-2 cells. Most of the mutations within the external domain of the v-fms-encoded protein eliminated focus formation on Rat-2 cells; three of these mutations interfered with the glycosylation of the v-fms protein and interfered with formation of the mature gp140fms. One mutation in the external domain led to cell surface expression of v-fms protein even in the absence of complete glycosylational processing. Cell surface expression of mutated v-fms protein is probably necessary, but is not sufficient, for cell transformation since mutant v-fms protein was found on the surface of several nontransformed cell lines. Mutations that were introduced within the external domain had little effect on in vitro kinase activity, whereas mutations within the cytoplasmic domain all had strong inhibitory effects on this activity.
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PMID:Analysis of functional domains of the v-fms-encoded protein of Susan McDonough strain feline sarcoma virus by linker insertion mutagenesis. 282 25

Amplification and expression of 16 protooncogenes were examined in 12 established small cell lung cancer (SCLC) cell lines. Seven of 12 cell lines showed a 20- to 35-fold amplification of the c-myc oncogene, 3 cell lines showed an 80- to 130-fold amplification of N-myc oncogene, and one cell line had a simultaneous amplification of the c-myb and N-myc oncogene. In this cell line both oncogenes were transcriptionally highly active at the same time. A variant subpopulation of SCLC expressed an 8.5-kilobase v-fms homologous transcript at high levels but without amplification of the c-fms gene. All cell lines examined had similar RNA levels of the N-ras, Ki-ras, Ha-ras, and c-raf1 oncogenes. DNA amplification, however, was undetectable. The protooncogenes c-fes, c-fos, and c-erbB were expressed very weakly and the transcripts of the oncogenes c-mos, c-sis, c-erbA, c-src, and c-abl were not observed in any of the 12 SCLC-cell lines. From these data we conclude that beyond the oncogenes myc and myb, oncogenes whose gene products are GTP binding proteins and phosphokinases may also be necessary to develop and keep the malignant state of SCLC. The v-fms homologous transcript found may be involved in the transition of the classic cell type to the variant cell type of SCLC.
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PMID:Amplification and expression of protooncogenes in human small cell lung cancer cell lines. 282 28

The gene product of the viral proto-oncogene v-fms, associated with the feline sarcoma virus (SM-FeSV), is a glycoprotein of 170 kd with associated tyrosine kinase activity. The murine c-fms proto-oncogene produces a similar glycoprotein of 165 kd and has been implicated as a similar, if not identical, molecule to the cell surface receptor of the hematopoietic growth factor CSF-1. Employing a v-fms probe in an in situ hybridization assay we examined the expression of c-fms transcripts in a population of purified granulocyte-macrophage progenitor cells (CFU-GM). Using this approach, which requires only 10-20 thousand cells, we demonstrate that 53% of the cells in the purified CFU-GM containing fraction (FR-28) express c-fms transcripts. In the presence of natural purified CSF-1, 51% +/- 3% of FR-28 cells form colonies or clusters in a semi-solid culture assay system. 94% of the colonies and clusters stimulated by CSF-1 were morphologically macrophage in nature. In addition, 84% +/- 4% of FR-28 cells formed colonies and clusters when stimulated with pokeweed mitogen spleen cell conditioned medium (PWMSCM) in a similar in vitro assay (35% granulocyte, 29% macrophage and 39% mixed granulocyte/macrophage colonies). These results indicate there is a correlation between the responsiveness of CFU-GM progenitor cells to CSF-1 and the expression of c-fms RNA.
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PMID:Correlation between CSF-1 responsiveness and expression of (CSF-1 receptor) c-fms in purified murine granulocyte-macrophage progenitor cells (CFU-GM). 282 1

The macrophage colony-stimulating factor, CSF-1 (M-CSF), is a homodimeric glycoprotein required for the lineage-specific growth of cells of the mononuclear phagocyte series. Apart from its role in stimulating the proliferation of bone marrow-derived precursors of monocytes and macrophages, CSF-1 acts as a survival factor and primes mature macrophages to carry out differentiated functions. Each of the actions of CSF-1 are mediated through its binding to a single class of high-affinity receptors expressed on monocytes, macrophages, and their committed progenitors. The CSF-1 receptor (CSF-1R) is encoded by the c-fms proto-oncogene, and is one of a family of growth factor receptors that exhibits an intrinsic tyrosine-specific protein kinase activity. Transduction of c-fms sequences as a viral oncogene (v-fms) in the McDonough (SM) and HZ-5 strains of feline sarcoma virus has resulted in alterations in receptor coding sequences that affect its activity as a tyrosine kinase and provide persistent signals for cell growth in the absence of its ligand. The genetic alterations in the c-fms gene that unmask its latent transforming potential abrogate its lineage-specific activity and enable v-fms to transform a variety of cells that do not normally express CSF-1 receptors.
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PMID:Colony-stimulating factor-1 receptor (c-fms). 285 67

Northern blot analysis was used to assess the level of expression of five protooncogenes and histone H3 in the bone marrow cells of patients with acute nonlymphocytic leukemia (ANLL). The relationship between the level of gene expression and the clinical characteristics of the disease and response to therapy was studied. The levels of expression of c-myc and c-myb are weakly correlated and are unrelated to French-American-British (FAB) type of ANLL. The levels of expression of c-fms, c-fes, and c-fos are highly correlated with each other and are highest in leukemia with a monocytic component (c-fms v FAB = .71, c-fes v FAB = .75). High levels of c-myc expression are associated with a high probability of not responding to remission induction therapy (P = .004). The converse is true for c-fms expression levels. High levels of expression of c-myc or c-myb are associated with short remissions (P = .059 and .065, respectively), perhaps because they are associated with a high capacity for leukemic cell self-renewal and/or an inability of leukemic cells to differentiate in response to chemotherapy.
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PMID:Protooncogene expression and the clinical characteristics of acute nonlymphocytic leukemia: A Leukemia Intergroup pilot study. 291 Mar 63

A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c-fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines.
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PMID:Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines. 291 75

The gene product of the viral proto-oncogene v-fms, associated with the feline sarcoma virus (SM-FeSV), is a glycoprotein of 170 kd with associated tyrosine kinase activity. The murine c-fms proto-oncogene produces a similar glycoprotein of 165 kd and has been implicated as a similar, if not identical, molecule to the cell surface receptor of the hematopoietic growth factor CSF-1. Employing a v-fms probe in an in situ hybridization assay we examined the expression of c-fms transcripts in a population of purified granulocyte-macrophage progenitor cells (CFU-GM). Using this approach, which requires only 10-20 thousand cells, we demonstrate that 53% of the cells in the purified CFU-GM containing fraction (FR-28) express c-fms transcripts. In the presence of natural purified CSF-1, 51% +/- 3% of FR-28 cells form colonies or clusters in a semi-solid culture assay system. 94% of the colonies and clusters stimulated by CSF-1 were morphologically macrophage in nature. In addition, 84% +/- 4% of FR-28 cells formed colonies and clusters when stimulated with pokeweed mitogen spleen cell conditioned medium (PWMSCM) in a similar in vitro assay (35% granulocyte, 29% macrophage and 39% mixed granulocyte/macrophage colonies). These results indicate there is a correlation between the responsiveness of CFU-GM progenitor cells to CSF-1 and the expression of c-fms RNA.
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PMID:Correlation between CSF-1 responsiveness and expression of (CSF-1 receptor) c-fms in purified murine granulocyte-macrophage progenitor cells (CFU-GM). 296 81


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