Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene.
Retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. Indeed, almost 90% of mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/He mice show upregulation of Int protooncogenes. We have analyzed three different MMTV variants [MMTV(C3H), MMTV(HeJ), and a genetically engineered MMTV hybrid provirus (HP)] for tumorigenicity in mice from two distinct genetic backgrounds. All three viruses were tumor causing in BALB/cJ mice. However, only MMTV(C3H), but not MMTV(HeJ) or HP, induced mammary tumors in C3H/He mice. All of the viruses were infectious on either background and up-regulated expression of Int genes in tumors they induced. Like HP, MMTV(HeJ) was found to be a genetic recombinant between endogenous Mtv1 provirus and exogenous MMTV(C3H). Sequence comparison of MMTV variants linked the tumorigenicity of MMTV(C3H) to the gag region of the retrovirus.
Hook
L M
LM
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Agafonova
Y
Y
Ross
S R
SR
Turner
S J
SJ
Golovkina
T V
TV
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D015750:Genes, gag; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000472:pathogenicity; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016415:Sequence Alignment