Expression of intracisternal A-particle retrotransposons in primary tumors of oncogene-expressing transgenic mice

Abstract

Intracisternal A-Particle (IAP) sequences are endogenous retrovirus-like mobile elements, present at 1000 copies in the mouse genome. These elements transpose in a replicative manner via an RNA intermediate and its reverse transcription, and their transposition should therefore be tightly controlled by their transcription level. The in vivo pattern of expression of these potentially mutagenic elements had previously been analysed in normal mice, and we have now investigated their expression in transgenic mice carrying different oncogenes (e.g. c-myc, v-Ha-ras, SV40 T-antigen) under tissue-specific promoters and disclosing tumors within the brain, the mammary or salivary glands, or the lymphoid organs. Northern blot analysis of IAP expression within the resulting tumors demonstrates a lack of significant and/or systematic effect of v-Ha-ras and SV40 T-antigen expression, but a systematic IAP induction in the myc-induced tumors. In this case, however, analysis of double transgenic mice obtained by crossing the tumor-prone mice with previously described transgenic mice carrying IAP reporter genes did not provide any evidence for induction of the IAP transgenes, therefore strongly suggesting that c-myc expression had an effect on only a limited number of IAP sequences--most probably depending on their position and/or methylation state. These results strengthen the importance of in vivo studies for a correct appraisal of complex biological processes, and moderate previous conclusions derived from in vitro analyses on the general activation of IAPs by oncogenes and on the role of these transposable elements in tumorigenesis.