Proviral unit II of endogenous mouse mammary tumour virus is selectively amplified and expressed in C57B1/10 mammary tumours induced by non-viral carcinogens

Abstract

Restriction enzyme analysis and molecular hybridization assay of DNA isolated from C57B1/10 mammary adenocarcinomas induced by a combination of dimethylbenzanthracene, oestrogen, and prolactin, revealed the presence of four extra copies of endogenous mouse mammary tumour virus (MMTV). PstI restriction pattern of the amplified proviral sequences indicated their identity with the proviral Unit II of endogenous MMTV. The amplified proviruses are hypomethylated and expressed in a hormone-dependent fashion. Their internal structure is slightly modified, since an additional EcoRI recognition site is present within the proviral genomic DNA. Selective amplification of Unit II MMTV provirus in the course of mammary tumourigenesis initiated by chemical carcinogens and hormones is compatible with the accepted multifactorial nature of this process, and is interpreted in terms of the insertional mutagenesis model for MMTV-induced oncogenesis. However, sequences of cellular DNA, adjacent to the amplified Unit II proviruses, show no homology to the integration domains int-1 and int-2 common to exogenous MMTV.