PMID- 11245493 OWN - NLM STAT- MEDLINE DCOM- 20010329 LR - 20220317 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 61 IP - 4 DP - 2001 Feb 15 TI - Identification of a proviral structure in human breast cancer. PG - 1754-9 AB - Involvement of a virus similar to mouse mammary tumor virus (MMTV) in human breast cancer has long been postulated but never demonstrated. We have detected by PCR a 660-bp sequence similar to the env gene of MMTV but not to the known endogenous viruses, in 38% of human breast cancers examined (Wang et al., Cancer Res., 55: 5173-5179, 1995). This sequence was expressed in 66% of the env-positive tumors as detected by reverse transcription-PCR (Wang et al., Clin. Cancer Res., 4: 2565-2568, 1998). In this article we report the amplification of a whole proviral structure from each of two human breast carcinomas that were env positive. Using nested extra-long PCR and primers from specific MMTV sequences, overlapping env-long terminal repeat (LTR), LTR-gag, gag-pol, and pol-env segments were successfully amplified. The 9.9-kb provirus is 95% homologous to MMTV but only 57% to human endogenous retrovirus K10 in 3.5 kb of the gag and pol genes. The provirus displays typical features of a replication competent virus, plus the open reading frame for the superantigen and the glucocorticoid responsive element. Fluorescence in situ hybridization with a 2.7-kb env-LTR sequence of an env-positive breast cancer cell line revealed that the sequence is inserted in several chromosomes but not in chromosomes from normal breast cells. The origin of the MMTV-like sequences is uncertain. Because they are undetectable in normal tissues, because the similarity between the two isolates is high (96%), and because they maintain open reading frames, they appear to be exogenous. FAU - Liu, B AU - Liu B AD - Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. FAU - Wang, Y AU - Wang Y FAU - Melana, S M AU - Melana SM FAU - Pelisson, I AU - Pelisson I FAU - Najfeld, V AU - Najfeld V FAU - Holland, J F AU - Holland JF FAU - Pogo, B G AU - Pogo BG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Fusion Proteins, gag-pol) RN - 0 (Viral Proteins) RN - 145715-39-5 (gene 9 protein, Rotavirus B) SB - IM MH - Breast Neoplasms/*virology MH - Cloning, Molecular MH - Endogenous Retroviruses/genetics MH - Fusion Proteins, gag-pol/genetics MH - Genes, env/genetics MH - Genes, gag/genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mammary Tumor Virus, Mouse/genetics MH - Polymerase Chain Reaction MH - Proviruses/*genetics MH - Sequence Homology, Nucleic Acid MH - Terminal Repeat Sequences MH - Tumor Cells, Cultured MH - Viral Proteins EDAT- 2001/03/14 10:00 MHDA- 2001/04/03 10:01 CRDT- 2001/03/14 10:00 PHST- 2001/03/14 10:00 [pubmed] PHST- 2001/04/03 10:01 [medline] PHST- 2001/03/14 10:00 [entrez] PST - ppublish SO - Cancer Res. 2001 Feb 15;61(4):1754-9.