Possibilities of a viral etiology for human breast cancer. A review

• Published in: Biological trace element research Vol. 56; no. 1; pp. 131 - 142
• Main Authors: Pogo, B G, Holland, J F
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.01.1997
• Subjects: AIDS/HIV; Animals; Breast cancer; Breast Neoplasms - etiology; Breast Neoplasms - virology; Cloning; Deoxyribonucleic acid; Disease Models, Animal; DNA; Female; Genes; Genes, env; Humans; Mammary Neoplasms, Experimental - etiology; Mammary Neoplasms, Experimental - virology; Mammary Tumor Virus, Mouse - genetics; Mammary Tumor Virus, Mouse - isolation & purification; Mammary Tumor Virus, Mouse - pathogenicity; Mice; Mouse mammary tumor virus; Retroviridae - genetics; Retroviridae - isolation & purification; Retroviridae - pathogenicity; Retrovirus; Viral infections
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/BF02778989

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.