Imbalanced expression of cellular nuclear oncogenes caused by v-sis/PDGF-2.
Two murine cell lines that overexpress v-sis/PDGF-2 were used to study the mechanism of cell transformation by SSV (simian sarcoma virus). In contrast to the parental cells that are phenotypically normal and serum-dependent for growth, v-sis-overexpressing cells grow in PDGF-free plasma medium, are unable to enter the G0 state and are highly tumorigenic. Analysis of the expression of some growth factor-induced early response genes in v-sis-overexpressing cells revealed: (a) high and constitutive c-myc mRNA levels in SSV-NRK cells; (b) unaltered levels of fra-1, fos B, jun B and krox 20 transcripts; (c) high and constitutive FOS staining due to c-FOS and FOS-related protein(s); (d) constitutive c-JUN and higher JUN D expression. These results are compatible with a model in which endogenous production of v-sis/PDGF-2 leads to deregulated expression of key cellular transregulators that, in turn, alter the cells' transcriptional program leading to the transformed state and malignancy.
Departamento de Bioquímica, Universidade de São Paulo, Brazil.
M H
MH
Sonobe
R
R
Bravo
M S
MS
Armelin
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics; D051767:Early Growth Response Protein 2; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D051379:Mice; D008807:Mice, Inbred BALB C; D020575:Oncogene Proteins v-sis; D009857:Oncogenes; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D020575:Oncogene Proteins v-sis; D010982:Platelet-Derived Growth Factor; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D013936:Thymidine