De-regulation of endogenous retrotransposons in mouse mammary carcinomas of diverse etiologies

Abstract

Of the several families of endogenous retrovirus-like elements present in the mouse genome, only mouse mammary tumor virus has been analyzed for its role in mammary carcinogenesis. Very little is known about the expression and activities of other retro-elements in normal and malignant mammary epithelium. We have begun investigating the possible involvement of the 3 retrotransposons, intracisternal A particles (IAPs), murine-leukemia-virus-related (MuLVr) elements, and VL30 sequences, in neoplastic progression of the mammary gland in BALB/c mice. The purpose of the present study was to determine which of these elements was active in primary mammary carcinomas induced by chemical, hormonal and viral agents. Each of these cancers had aberrant expression of at least one of the latter retrovirus-like components. IAP and/or MuLVr sequences were over-expressed 3 to 100-fold in most of the tumors as compared with normal mammary tissue, whereas VL30 expression was markedly decreased by 5- to 35-fold in almost all of the neoplasms. Our results thus demonstrate that substantial changes in the expression of one or more of these 3 families of endogenous retrotransposons are triggered during mouse mammary tumorigenesis, regardless of etiology. Direct involvement of IAPs and MuLVr elements in neoplastic progression by transposition and insertional mutagenesis in the genome of several hematopoietic cell types has already been demonstrated. Their elevated expression in many mammary carcinomas suggests that these retrotransposons may also be potential participants in some pathways of mouse mammary carcinogenesis.