Possibilities of a viral etiology for human breast cancer. A review.
Previous studies related mouse mammary tumor virus (MMTV) to human breast cancer. However, the presence of human endogenous retroviruses (HERs) confounded these results. We selected a 660-bp sequence of the MMTV env gene with low homology to HER (or any other known gene) and searched for a sequence homologous to it, using the polymerase chain reaction (PCR). The 660-bp sequence was detected in 131 (39%) of 335 unselected breast cancers, in 2 (6.9%) of 29 fibroadenomas, and in 2 (1.65%) of 121 normal breast specimens. The sequence was not present in normal tissues, or in other human cancers or cell lines. Cloning and sequencing of the 660-bp sequence revealed that it is 95-98% homologous to MMTV env gene, but not the known HERs or other viral or human gene. Southern blot hybridization using labeled cloned sequences demonstrated that the 660-bp sequence was present in very low copy number as a 6-8 kb EcoRI fragment only in breast cancer samples and in some of the human breast cancer cell lines that were positive by PCR. Preliminary experiments using reverse transcriptase (RT)-PCR indicated that expression of the 660-bp sequence can be detected in 65% of the positive tumors. We were also able to identify in breast cancer DNA a segment of 1.6 kb comprising LTR and env gene sequences, which are homologous to MMTV, but not to the HERs. The origin of the MMTV-like sequences in tumor DNA could be the result of integrated MMTV-like sequences derived from a human mammary virus.
Pogo
B G
BG
Department of Medicine, Mount Sinai School of Medicine, CUNY, New York, NY 10029, USA.
Holland
J F
JF
D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology* / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D015752:Genes, env; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D051379:Mice; D012190:Retroviridae / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity