Transformation of liver by SV-40 T-antigen in transgenic mice is unaffected by metallothionein.
Transgenic mice expressing excess metallothionein-I and SV-40 T-antigen were generated to test the hypothesis that metallothionein may influence the rate of neoplastic transformation induced by T-antigen within the liver. The livers of the double transgenic mice grew at the same rate (to 32% body weight), had similar morphological and histological appearance, had similar chromosomal instability, and released identical amounts of serine and alanine aminotransferases into the blood as mice bearing SV-40 T-antigen alone, despite the fact that metallothionein levels were elevated five- to ten-fold. We conclude that elevated levels of metallothionein-I do not influence either the initial hyperplasia or the subsequent neoplastic transformation that is induced by T-antigen, which is thought to act by sequestering the P53 and retinoblastoma gene products.
Quaife
C J
CJ
Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA. quaife@u.washington.edu
Veith
G C
GC
Palmiter
R D
RD
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D002471:Cell Transformation, Neoplastic; D003300:Copper / Q000032:analysis; D004247:DNA / Q000032:analysis; D008099:Liver / Q000473:pathology* / Q000502:physiology; D008668:Metallothionein / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D011401:Promoter Regions, Genetic; D012709:Serum Albumin / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics*; D015032:Zinc / Q000032:analysis
D000957:Antigens, Viral, Tumor; D012709:Serum Albumin; D003300:Copper; D004247:DNA; D008668:Metallothionein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D015032:Zinc