A mouse mammary tumor virus-like long terminal repeat superantigen in human breast cancer.
We previously reported a 660-bp mouse mammary tumor virus (MMTV)-like env gene sequence in approximately 38% of human breast cancer DNA, but not in normal breasts or other tumors. This MMTV-like env gene sequence was expressed in 66% of the env gene-positive human breast cancers. An entire proviral structure was identified in human breast cancer DNA with high homology to MMTV and low homology to known human endogenous retrovirus. MMTV-like long terminal repeat (LTR) sequences were also detected in 41.5% of human breast cancers. They contain hormone-responsive elements, TEF-1 family elements, and the open reading frame for the superantigen (SAg). We have now amplified and sequenced MMTV-like sag sequences from 10 human breast cancers, and we found that they are highly homologous to those of MMTV. However, deletions and insertions at the COOH-terminal of sag were observed. The immune function of the human MMTV-like LTR SAg was also investigated. The sag gene was cloned and expressed in a human B-cell line (Ramos). T-cell proliferation and cytokine releasing assays were performed after cocultivation of T cells with irradiated Ramos SAg-expressing cells. The results indicate that expression of the human SAg stimulates T-cell activation in vitro, as the mouse SAg does. Because the T-cell responses in vitro are considered similar to those in vivo, these results suggest that the human LTR SAg might also play a role in human breast carcinogenesis.
Wang
Yue
Y
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Jiang
Jian-Dong
JD
Xu
Dongping
D
Li
Yan
Y
Qu
Chunfeng
C
Holland
James F
JF
Pogo
Beatriz G-T
BG
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018089:Superantigens / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D020079:Terminal Repeat Sequences; D014162:Transfection
D016207:Cytokines; D018089:Superantigens