Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene

Journal Article · Sat Apr 01 04:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.8.2693· OSTI ID:5162359

Pech, M; Gazit, A; Arnstein, P; Aaronson, S A ^[1]

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1. National Cancer Institute, Bethesda, MD (USA)

A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Proviruses in each fibrosarcoma analyzed had lost 149 nucleotides downstream of the PDGF-B coding region. This deletion originated from an alternative or aberrant splice event that occurred within exon 7 of the PDGF-B gene and mimicked the v-sis oncogene. Thus, deletion of this region may be necessary for efficient retrovirus replication or for more potent transforming function. Evidence that the normal growth factor coding sequence was unaltered derived from RNase protection studies and immunoprecipitation analysis. Tumors were generally polyclonal but demonstrated clonal subpopulations. Moreover, tumor-derived cell lines became monoclonal within a few tissue culture passages and rapidly formed tumors in vivo. These findings argue that overexpression of the normal human PDGF-B gene product under retrovirus control can induce the fully malignant phenotype.

• OSTI ID: 5162359
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:8; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBOXYLIC ACIDS
CARCINOGENESIS
CYSTEINE
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DNA HYBRIDIZATION
DRUGS
EVEN-ODD NUCLEI
FIBROSARCOMAS
GENE REGULATION
GENES
GROWTH FACTORS
HYBRIDIZATION
IN VIVO
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MATERIALS
METHIONINE
MICE
MICROORGANISMS
MITOGENS
NEONATES
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
ONCOGENES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PARASITES
PATHOGENESIS
PROTEINS
RADIOISOTOPES
RODENTS
SARCOMAS
SULFUR 35
SULFUR ISOTOPES
THIOLS
VERTEBRATES
VIRUSES