EXPRESSION OF INTRACISTERNAL A-PARTICLE RETROTRANSPOSONS IN PRIMARY TUMORS OF ONCOGENE-EXPRESSING TRANSGENIC MICE

Intracisternal A-Particle (IAP) sequences are endogenous retrovirus-li ke 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 b e tightly controlled by their transcription level, The in vi,to patter n of expression of these potentially mutagenic elements had previously been analysed in normal mice, and we have now investigated their expr ession 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 lymph oid organs, Northern blot analysis of IAP expression within the result ing tumors demonstrates a lack of significant and/or systematic effect of v-Ha-ras and SV40 T-antigen expression, but a systematic IAP induc tion in the myc-induced tumors, In this case, however, analysis of dou ble transgenic mice obtained by crossing the tumor-prone mice with pre viously described transgenic mice carrying IAP reporter genes did not provide any evidence for induction of the IAP transgenes, therefore st rongly suggesting that c-myc expression had an effect on only a limite d number of IAP sequences - most probably depending on their position and/or methylation state, These results strengthen the importance of i n 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 t ransposable elements in tumorigenesis.