Rapid, complete and reversible transformation by v-sis precedes irreversible transformation.
v-sis is the oncogene of simian sarcoma virus, but whether tumor growth is maintained by v-sis expression alone or requires additional changes is unknown. To distinguish these possibilities we studied a model of reversible transformation including tumorigenicity using NIH3T3 cells bearing a metallothionein promoter-v-sis construction. Cells subcultured from 10 out of 18 tumors from athymic mice, all less than 0.1 g and less than or equal to 21 days in age, reverted to a normal phenotype but exhibited transformation upon addition of zinc as judged by morphology, growth rate, saturation density and anchorage independence of growth. Thus, activation of v-sis alone is sufficient for initiation and early autocrine-based growth of tumors. However, the cells from the remaining and predominantly larger, 0.5 +/- 0.7 g, tumors did not revert and exhibited zinc-independent transformation as judged by the same criteria. Southern analysis and examination of the regulation of v-sis product expression in cells derived from these tumors showed no change in zinc-dependent and reversible regulation of v-sis sequences. These results suggest that subsequent tumor growth strongly favors acquisition of additional irreversible change(s) in the tumor cell genome at high frequency (44%). Thus an early event of a multistep process stimulated by v-sis-dependent transformation best accounts for the sum of results.
Mercola
D
D
Department of Pathology, University of California, San Diego, La Jolla 92093.
Carpenter
P M
PM
Grover-Bardwick
A
A
Mercola
M
M
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D020575:Oncogene Proteins v-sis; D009857:Oncogenes; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D015032:Zinc / Q000494:pharmacology
D020575:Oncogene Proteins v-sis; D015682:Retroviridae Proteins, Oncogenic; D015032:Zinc