Home LiteratureArticle Details
PMID: 3017700 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The phenotypic characteristics of simian sarcoma virus-transformed human fibroblasts suggest that the v-sis gene product acts solely as a PDGF receptor agonist in cell transformation.

The EMBO journal ·Vol. 5 ·No. 7 ·1986-07-00 ·Pages 1535-41

Johnsson A, Betsholtz C, Heldin CH, Westermark B

Abstract

Previous studies have indicated that the oncogene v-sis of simian sarcoma virus (SSV) encodes a growth factor that is structurally and functionally similar to platelet-derived growth factor (PDGF). In the present investigation we have analysed the phenotypic characteristics of human foreskin fibroblasts transformed by SSV. It was found that the PDGF receptors were extensively down-regulated. This finding is consistent with a high, local, extracellular concentration of a PDGF-like factor, synthesized by the transformed cell. The receptors were up-regulated by suramin, a drug that is known to dissociate PDGF and the v-sis product from the PDGF receptors. A cell-associated v-sis product of mol. wt 24,000 was identified by immunoprecipitation with PDGF antibodies; release of this component was induced by a high concentration of exogenous PDGF, indicating that a fraction of the product is associated with the PDGF receptors. SSV was not found to be an immortalizing virus; when serially passaged, SSV-transformed cells had essentially the same life-span as their non-transformed counterparts. Moreover, SSV did not induce growth in soft agar beyond the level afforded by exogenously added PDGF. Thus, the present study favors the notion that SSV transformation is mediated by a growth factor that mimics PDGF but has no further cellular effects.

MeSH Terms
Cell Division Cell Line Cell Transformation, Neoplastic Fibroblasts/metabolism Genes Genes, Viral Humans Kinetics Male Molecular Weight Oncogene Proteins, Viral/genetics,metabolism Oncogenes Phenotype Platelet-Derived Growth Factor/metabolism Receptors, Cell Surface/metabolism Receptors, Platelet-Derived Growth Factor Retroviridae/genetics Sarcoma Virus, Woolly Monkey/genetics Skin
Chemicals
Oncogene Proteins, Viral Platelet-Derived Growth Factor Receptors, Cell Surface Receptors, Platelet-Derived Growth Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Johnsson A
Betsholtz C
Heldin C H
Westermark B
References (34)
34 references, click to expand
  1. The growth capacity of normal and Rous-virus-transformed chicken fibroblasts in vitro.
    Int J Cancer. 1970 Nov 15;6(3):323-32 PMID: 4321010
  2. Antibodies against platelet-derived growth factor inhibit acute transformation by simian sarcoma virus.
    Nature. 1985 Oct 3-9;317(6036):438-40 PMID: 2995828
  3. Aging of human fibroblasts in vitro: surface features and behavior of aging WI 38 cells.
    Mech Ageing Dev. 1975 Mar-Apr;4(2):147-58 PMID: 1152546
  4. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma.
    J Cell Biol. 1975 Dec;67(3):835-51 PMID: 811671
  5. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro.
    Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435-9 PMID: 172908
  6. Autocrine secretion and malignant transformation of cells.
    N Engl J Med. 1980 Oct 9;303(15):878-80 PMID: 7412807
  7. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction.
    Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494-8 PMID: 6251462
  8. Demonstration of an antibody against platelet-derived growth factor.
    Exp Cell Res. 1981 Dec;136(2):255-61 PMID: 6171440
  9. Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation.
    J Biol Chem. 1982 Apr 25;257(8):4216-21 PMID: 6279627
  10. Platelet-derived growth factor. III. Identification of a platelet-derived growth factor receptor by affinity labeling.
    J Biol Chem. 1982 May 10;257(9):5172-6 PMID: 6279660
  11. Platelet-derived growth factor: identification of constituent polypeptide chains.
    Biochem Biophys Res Commun. 1982 Jan 15;104(1):66-74 PMID: 7073684
  12. Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28sis.
    Proc Natl Acad Sci U S A. 1983 Feb;80(3):731-5 PMID: 6298772
  13. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor.
    Science. 1983 Jul 15;221(4607):275-7 PMID: 6304883
  14. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus.
    Nature. 1983 Jul 7-13;304(5921):35-9 PMID: 6306471
  15. Cellular responsiveness to growth factors correlates with a cell's ability to express the transformed phenotype.
    Cell. 1983 Jul;33(3):931-8 PMID: 6307528
  16. Characterization of the receptor for platelet-derived growth factor on human fibroblasts. Demonstration of an intimate relationship with a 185,000-Dalton substrate for the platelet-derived growth factor-stimulated kinase.
    J Biol Chem. 1983 Aug 25;258(16):10054-61 PMID: 6309764
  17. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor.
    Nature. 1983 Oct 13-19;305(5935):605-8 PMID: 6312326
  18. Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus.
    Science. 1984 Feb 3;223(4635):487-91 PMID: 6318322
  19. Synthesis of a PDGF-like growth factor in human glioma and sarcoma cells suggests the expression of the cellular homologue to the transforming protein of simian sarcoma virus.
    Biochem Biophys Res Commun. 1983 Nov 30;117(1):176-82 PMID: 6318746
  20. Growth factor-induced proliferation of human fibroblasts in serum-free culture depends on cell density and extracellular calcium concentration.
    J Cell Physiol. 1984 Feb;118(2):203-10 PMID: 6607257
  21. Platelet-derived growth factor receptors form a high affinity state in membrane preparations. Kinetics and affinity cross-linking studies.
    J Biol Chem. 1984 Apr 25;259(8):5287-94 PMID: 6325430
  22. Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor.
    Cell. 1984 May;37(1):123-9 PMID: 6327048
  23. Growth factors: mechanism of action and relation to oncogenes.
    Cell. 1984 May;37(1):9-20 PMID: 6373015
  24. The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor.
    EMBO J. 1984 May;3(5):921-8 PMID: 6329745
  25. Cellular transformation by coordinated action of three peptide growth factors from human platelets.
    Nature. 1984 Jun 28-Jul 4;309(5971):804-6 PMID: 6330562
  26. Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors.
    Proc Natl Acad Sci U S A. 1984 Dec;81(23):7466-70 PMID: 6095298
  27. Requirement for a signal sequence in biological expression of the v-sis oncogene.
    Science. 1984 Dec 7;226(4679):1197-9 PMID: 6095451
  28. Purification and properties of porcine platelet-derived growth factor.
    EMBO J. 1984 Dec 1;3(12):2963-7 PMID: 6526008
  29. Autocrine growth factors and cancer.
    Nature. 1985 Feb 28-Mar 6;313(6005):745-7 PMID: 3883191
  30. Platelet-derived growth factor agonist activity of a secreted form of the v-sis oncogene product.
    Proc Natl Acad Sci U S A. 1985 Mar;82(6):1721-5 PMID: 2984666
  31. In vitro mutagenesis of the v-sis transforming gene defines functional domains of its growth factor-related product.
    Proc Natl Acad Sci U S A. 1985 Aug;82(16):5295-9 PMID: 2991916
  32. The v-sis/PDGF-2 transforming gene product localizes to cell membranes but is not a secretory protein.
    EMBO J. 1985 Jul;4(7):1783-92 PMID: 2992941
  33. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis.
    Nature. 1985 Aug 22-28;316(6030):748-50 PMID: 4033772
  34. Role of diffusion boundary layer in contact inhibition of growth.
    Nature. 1973 Nov 23;246(5430):200-3 PMID: 4586793
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1986-07-00
Pages
1535-41
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1166977
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com