RETROVIRUS-LIKE PARTICLES RELEASED FROM THE HUMAN BREAST-CANCER CELL-LINE T47-D DISPLAY TYPE-B-RELATED AND TYPE-C-RELATED ENDOGENOUS RETROVIRAL SEQUENCES

The human mammary carcinoma cell line T47-D releases retrovirus-like p articles of type B morphology in a steroid-dependent manner (I. Keydar , T. Ohno, R. Nayak, R. Sweet, F. Simoni, F. Weiss, S. Karby, R. Mesa- Tejada, and S. Spiegelman, Proc. Natl. Acad. Sci. USA 81:4188-4192, 19 84). Furthermore, reverse transcriptase (RT) activity is found to be a ssociated with particle preparations. Using a set of degenerate primer s derived from a conserved region of retroviral pol genes, we repeated ly amplified three different retroviral sequences (MLN, FRD, and FTD) from purified T47-D particles in several RT-PCR experiments. Screening of a human genomic library and Southern blot analysis revealed that t hese sequences are of endogenous origin. ERV-MLN represents a multicop y family of human endogenous retroviral elements (HERVs) with two clos ely related copies and up to 20 more distantly related members. In con trast, ERV-FRD and ERV-FTD comprise only one copy and five to seven re lated elements per haploid human genome. DNA sequence analysis of the proviral pol region of ERV-MLN revealed an uninterrupted stretch of 24 1 amino acids that shows 65% identity with the RT of the type B-relate d HERV designated HERV-K10. ERV-FRD and ERV-FTD are defective type C-r elated HERVs. The pol gene of ERV-FRD displays a nucleotide homology o f 54% to the gibbon ape leukemia virus, and the pol gene of ERV-FTD is about 67% homologous to members of the RTVL-I family of HERVs. Our re sults thus indicate that the retroviral particles released by the brea st cancer cell line T47-D are probably generated by complementation of several endogenous proviruses and can package retroviral transcripts of different origins.