Identification of a proviral structure in human breast cancer.
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.
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
B
B
Liu
Y
Y
Wang
S M
SM
Melana
I
I
Pelisson
V
V
Najfeld
J F
JF
Holland
B G
BG
Pogo
D001943:Breast Neoplasms / Q000821:virology*; D003001:Cloning, Molecular; D020077:Endogenous Retroviruses / Q000235:genetics; D015685:Fusion Proteins, gag-pol / Q000235:genetics; D015752:Genes, env / Q000235:genetics; D015750:Genes, gag / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D020079:Terminal Repeat Sequences; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D015685:Fusion Proteins, gag-pol; D014764:Viral Proteins; C071648:gene 9 protein, Rotavirus B