RETROVIRAL-LIKE SEQUENCES SPECIFICALLY EXPRESSED IN THE RAT OVARY DETECT GENETIC-DIFFERENCES BETWEEN NORMAL AND TRANSFORMED RAT OVARIAN SURFACE EPITHELIAL-CELLS

We have identified a repetitive DNA element in the rat genome that we demonstrate to be suitable to detect molecular genetic differences bet ween normal and malignantly transformed rat ovarian surface epithelial cells by genome scanning. With fluorescence in situ hybridization, we show that these elements are widely distributed in the rat genome, an d that a member of this family is present within a homogeneously stain ing chromosomal region of tumorigenic rat ovarian surface epithelial c ells. The homogeneously staining chromosomal region infers the presenc e of an amplified DNA sequence in the tumor cells, and we provide mole cular evidence for an, amplicon in this DNA by genome scanning using a probe related to these elements. Sequence analysis revealed that thes e elements have the structural features of retroviral DNA. We show tha t they are transcriptionally active in the rat ovary, but not in a wid e range of other normal rat tissues. In situ hybridization to ovarian tissue sections revealed that the elements are expressed in granulosa and theca interna cells and in the surface epithelial cells adjacent t o preovulatory follicles. Based on this property, we refer to these re troviral-like elements as ovary-specific transcribed sequences. Partia l sequence analysis of multiple members of this family and the range i n transcript sizes strongly suggest that multiple members of this retr ovirus-like family are transcriptionally active. We speculate that bin ding by one or a combination of ovary-specific transcription factors t o regulatory sequences within the genomic ovary-specific transcribed s equences units contributes to the tissue specificity of their expressi on.