Transcription of multiple exogenous mouse mammary tumor viruses in a single mammary tumor of an SHN mouse.
The SHN mouse strain, established in Japan independently from other mammary tumor-prone strains, is known to have a very high incidence of early-onset mammary tumors. In this study, we demonstrate that exogenous mouse mammary tumor virus (MMTV) plays a crucial role in early-onset mammary tumorigenesis in this strain. We subsequently isolated MMTV RNA from a mammary tumor of an SHN female mouse, reverse transcribed it, and amplified a 1.2-kb coding region of the long terminal repeat (LTR) by use of the polymerase chain reaction. The products were then subcloned into a pUC18 vector. Six clones were obtained, and their nucleotide sequences were determined. Nucleotide sequences of the six cloned LTRs indicated that two MMTVs are transcribed in the tumor. Both of them had point mutations and were different from known LTR sequences. Both LTRs had a potential open reading frame encoding 320 amino acids. The amino acid variabilities were predominantly between positions 280 and 320 codons when compared with deduced open reading frames. In contrast, only a few point mutations were detected in the regulatory area that contains five glucocorticoid elements, the nuclear factor-1 binding sites, the octamer consensus sequence, and the TATA box. Because point mutations occur more predominantly between positions 280 and 320, it is possible that mutations in this area endow MMTV with beneficial functions for propagation through mutational selection during tumorigenesis.
Koizumi
A
A
Department of Hygiene, Akita University School of Medicine, Japan.
Tsukada
M
M
Sugawara
K
K
Kusano
T
T
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D003062:Codon; D012367:RNA, Viral