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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Products of phosphatidylinositol turnover have recently been implicated as regulators of cell growth and differentiation. Transformation of cells in culture by infection with certain viruses (Rous sarcoma virus, Kirsten sarcoma virus, and polyoma virus) or by transfection with the oncogenes carried by these viruses affect the steady-state level of intermediates in the PI turnover pathway. In addition, immunoprecipitates of the transforming gene products of Rous sarcoma virus and polyoma virus contain activities of certain enzymes in the PI turnover pathway. We have previously reported that polyoma middle T immunoprecipitates can catalyze phosphorylation of PI to phosphatidylinositol-4-phosphate (PIP). This activity is not intrinsic to middle T or c-src but is due to a cellular enzyme that specifically associates with this complex. The PI kinase is found in immunoprecipitates of the middle T protein from polyoma viruses that are capable of cell transformation but does not associate with mutants of middle T defective in transformation suggesting that this association may be important for transformation.
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PMID:Oncogenes and phosphatidylinositol turnover. 243 50

Tumors which are induced in chickens by Rous sarcoma virus (RSV) usually grow progressively for several weeks and then regress. pp60src kinase activity was found to be reduced in cultured tumor cells which derived from regressing sarcomas by 60-75% as compared to progressively growing neoplasms. We further found that a cellular pp89 which co-precipitated with pp60src was largely diminished in tumor cells derived from regressing as compared with progressively growing sarcomas. In contrast, immunoprecipitation analyses from membrane or cytosol fractions did not reveal any significant differences between these 2 types of tumor cells in distribution of pp60src. Moreover, partial proteolysis or isoelectric focussing of labelled immunoprecipitated pp60src did not reveal major differences between the 2 tumor cell types. These data indicate that the lack of pp89 cell binding to pp60src in regressing sarcoma cells correlates well with the diminution of the pp60src kinase activity in these cells, but does not affect the transport of pp60src to the plasma membrane.
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PMID:Altered pp60src kinase activity in regressing tumors induced by Rous sarcoma virus. 243 33

A difference in affinity for a Nonidet P-40-insoluble cellular matrix was observed between the products of the viral and cellular src genes. It has previously been demonstrated that pp60v-src is associated with a detergent-insoluble matrix containing the cellular cytoskeleton (J. G. Burr, G. Dreyfuss, S. Penman, and J. M. Buchanan, Proc. Natl. Acad. Sci. USA 77:3484-3488, 1980). We observed a similar association of the transforming proteins of Fujinami sarcoma virus (P130gag-fps) and Yamaguchi 73 avian sarcoma virus (P90gag-yes), both of which are tyrosine-specific protein kinases. However, we found that the endogenous c-src product, pp60c-src, was not tightly bound to the detergent-insoluble matrix. This does not appear to have been due to differences in the cytoskeleton between transformed and nontransformed cells since pp60c-src was also solubilized by nonionic detergent in cells transformed by Rous sarcoma virus. This difference in the affinities of the v-src and c-src products for cytoskeletal proteins may contribute to the inability of pp60c-src to transform cells.
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PMID:pp60c-src has less affinity for the detergent-insoluble cellular matrix than do pp60v-src and other viral protein-tyrosine kinases. 243 5

The protein substrates for the tyrosine protein kinases in cells transformed by avian sarcoma viruses were analyzed by gel electrophoresis in combination with immunoblotting or immunoprecipitation by antibodies against phosphotyrosine. We found that greater than 90% of phosphotyrosine-containing cellular proteins can be immunoprecipitated by these antibodies. The level of phosphotyrosine-containing cellular proteins detectable by this method markedly increased upon transformation with Rous sarcoma virus, and more than 20 distinct bands of such proteins were found in lysates of Rous sarcoma virus-transformed cells. Most of these phosphotyrosine-containing proteins had not been identified by other methods, and their presence appeared to correlate with morphological transformation in cells infected with various Rous sarcoma virus mutants and Y73, PRCII, and Fujinami sarcoma viruses. However, considerably different patterns were obtained with cells infected with nontransforming Rous sarcoma virus mutants that encode nonmyristylated src kinases, indicating that most substrates that correlate with transformation can only be recognized by p60v-src associated with the plasma membrane.
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PMID:Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies. 246 69

Subcellular localization of potential substrates of a tyrosine-protein kinase, p60v-src, was analyzed by cell fractionation in combination with immunoblotting with antiphosphotyrosine antibody. In cells transformed by wild type Rous sarcoma virus, most phosphotyrosine-containing proteins were found both in plasma membranes and in a cytoplasmic matrix structure associated with plasma membranes and resistant to nonionic detergent extraction (plasma membrane matrix). A similar localization of phosphotyrosine-containing proteins was obtained in cells transformed by PRCII, Y73, or Fujinami sarcoma virus. On the other hand, in cells infected with Rous sarcoma virus mutants that encode nonmyristylated p60v-src, tyrosine phosphorylation was found mostly in proteins which were different from those identified in wild type-infected cells and were distributed to both plasma membrane and cytosolic fractions. These results suggest that most cellular substrate proteins, phosphorylation of some of which may be critical for the initiation of transformation, are present primarily in the plasma membrane-matrix structure.
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PMID:Localization of major potential substrates of p60v-src kinase in the plasma membrane matrix fraction. 249 23

Oncogenically transformed cells show reduced assembly of fibronectin-rich extracellular matrixes and diminished ability to adhere to fibronectin. The molecular bases of these phenotypic alteration are not fully understood. We report here alterations in the spectrum of integrins, including two fibronectin receptors, on oncogenic transformation of rodent cells. Transformation of rat1, NRK, and Nil8 cells by Rous sarcoma virus or by murine sarcoma viruses encoding ras oncogenes leads to reductions in the level of integrin alpha 5 beta 1, which is a well-defined fibronectin receptor, and of two other integrin receptors. In contrast, another receptor, alpha 3 beta 1, which is a polyspecific receptor for fibronectin, laminin, and collagen, is retained by transformed cells. These results provide explanations for earlier results concerning the interactions of extracellular matrix proteins with the surfaces of tumor cells and offer leads to further understanding of the altered adhesive and migratory behavior of malignant cells.
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PMID:Changes in integrin receptors on oncogenically transformed cells. 252 61

The cellular mutant B814 isolated from a Fischer rat cell line shows temperature-sensitivity of focus formation on infection with Moloney murine sarcoma virus (Mo-MSV) and Rous sarcoma virus (RSV). An RSV-transformed clone (S814-2) isolated from B814 cells shows temperature-sensitive transformed phenotypes for morphology, growth in soft agar, and glucose uptake. The expression, phosphorylation, and tyrosine kinase activity of pp60v-src in S814-2 were not affected at the nonpermissive temperature, and virus rescued from this clone had wild-type transforming ability, suggesting that a cellular factor altered in S814-2 is responsible for the cellular steps of transformation after the function of pp60v-src. In addition, the cellular 36K protein, a possible candidate as a target of pp60v-src, was phosphorylated at the nonpermissive temperature in S814-2, indicating that phosphorylation of the 36K protein is not correlated with transformed phenotypes.
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PMID:A rat mutant cell clone showing temperature-dependent transformed phenotypes with functional expression of the src gene product. 253 7

Two recovered avian sarcoma viruses (rASVs), rASV157 and rASV1702, encode src products which contain novel, nonmyristoylated N-terminal amino acids. These viruses transform chicken embryo fibroblasts and cause tumors in chicks. However, the tumors rASVs induce are small and regress within 2 weeks. To determine whether this regression results from weak tumorigenicity or from the active immunity of the host, we injected 1-week-old chicks with rASV and several days later injected the chicks with challenge virus of a different subgroup. Of the rASV1702-preinfected chicks challenged 5 days later with Rous sarcoma virus (RSV), 40% showed no subsequent tumor formation and 60% formed tumors which regressed within 1 week. The potency of this protective effect depended on the dosage of preinfection virus used and increased as the interval between preinfection and challenge infection was lengthened (when the interval was 9 days, none of the challenged chicks formed tumors). rASV157-preinfected chicks challenged with RSV after 9 days showed only partial protection: 42% formed tumors which regressed, whereas 58% formed tumors which continued to grow. Challenging rASV-preinfected chicks with Fujinami sarcoma virus or a RSV vector encoding the v-fps oncogene or polyomavirus middle T resulted in no suppression of tumor formation. Preinfection with src mutants or a RSV vector encoding polyomavirus middle T antigen, both of which induce slow-growing tumors, failed to elicit the protective effect. Finally, a novel N-terminal domain encoded by rASV1702 src was shown to be involved in but not sufficient for full protection. These data indicate that determinants on or induced by rASV157 and rASV1702 can elicit a potent protection against the tumorigenic potential of RSV-encoded p60v-src.
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PMID:Suppression of Rous sarcoma virus-induced tumor formation by preinfection with viruses encoding src protein with novel N termini. 254 64

Previous work from this laboratory has shown that preimmunization of syngeneic hosts with Rous sarcoma virus (RSV)-transformed cells elicits a strong immune response against the growth of transplantable RSV sarcomas, mediated by T lymphocytes expressing the surface phenotype of helper cell precursors (Prat, Di Renzo & Comoglio, 1983). This paper shows that anti-tumour immunity may be elicited in tumour-bearing animals by triggering an experimentally pre-amplified T-helper cell population at the site of tumour growth. Mice were treated with cyclophosphamide (which inactivates suppressor T cells) followed by skin sensitization to trinitrochlorobenzene (TNCB) according to a protocol that has been shown to induce an appreciably amplified generation of trinitrophenyl (TNP)-reactive helper T cells (Fujiwara et al., 1984). Five weeks after TNCB painting, mice were transplanted s.c. with a lethal dose of RSV-induced syngeneic sarcoma cells; the injection at the tumour site of TNCB induced the regression of the tumour in mice in which the TNP-helper cell population has been amplified, but not in controls, including those injected with a non-related hapten or sensitized to TNCB without inactivation of suppressors.
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PMID:Enhancement of immunity against RSV-induced sarcomas by generation of hapten-reactive helper T lymphocytes. 257 31

DNA-protein interactions involving enhancer and promoter sequences within the U3 regions of several avian retroviral long terminal repeats (LTRs) were studied by DNase I footprinting. The rat CCAAT/enhancer-binding protein, C/EBP, bound to all four viral LTRs examined. The Rous sarcoma virus binding site corresponded closely to the 5' limit of the LTR enhancer; nucleotides -225 to -188 were protected as a pair of adjacent binding domains. The Fujinami sarcoma virus LTR bound C/EBP at a single site at nucleotides -213 to -195. C/EBP also bound to the promoter region of the enhancerless Rous-associated virus-0 LTR at nucleotides -77 to -57. The avian myeloblastosis virus LTR bound C/EBP at three sites: nucleotides -262 to -246, -154 to -134, and -55 to -39. We have previously observed binding of C/EBP to an enhancer in the gag gene of avian retroviruses. A heat-treated nuclear extract from chicken liver bound to all of the same retroviral sequences as did C/EBP. Alignment of the avian retroviral binding sequences with the published binding sites for C/EBP in two CCAAT boxes and in the simian virus 40, polyoma, and murine sarcoma virus enhancers suggested TTGNNGCTAATG as a consensus sequence for binding of C/EBP. When two bases of this consensus sequence were altered by site-specific mutagenesis of the Rous sarcoma virus LTR, binding of the heat-stable chicken protein was eliminated.
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PMID:Avian retroviral long terminal repeats bind CCAAT/enhancer-binding protein. 272 92


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