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.
Sonobe
M H
MH
Departamento de Bioquímica, Universidade de São Paulo, Brazil.
Bravo
R
R
Armelin
M S
MS
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