Presence of mouse mammary tumour-like virus gene sequences may be associated with morphology of specific human breast cancer

Abstract

Background: Mouse mammary tumour virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible in-bred mice. MMTV-like env gene sequences, which indicate the presence of a replication-competent MMTV-like virus, have been identified in some human breast cancers, but rarely in normal breast tissues. However, no evidence for a causal role of an MMTV-like virus in human breast cancer has emerged, although there are precedents for associations between specific histological characteristics of human cancers and the presence of oncogenic viruses. Aim: To investigate the possibility of an association between breast cancer and MMTV-like viruses. Methods: Histological characteristics of invasive ductal human breast cancer specimens were compared with archival MMTV-associated mammary tumours from C3H experimental mice. The presence of MMTVlike env DNA sequences in the human breast cancer specimens was determined by polymerase chain reaction and confirmed by Southern hybridisation. Results: MMTV-like env gene sequences were identified in 22 of 59 (37.3%) human breast cancer specimens. Seventeen of 43 (39.5%) invasive ductal carcinoma breast cancer specimens and 4 of 16 (25%) ductal carcinoma in situ specimens had some histological characteristics, which were similar to MMTV-associated mouse mammary tumours. However, these similarities were not associated with the presence or absence of MMTV-like gene sequences in the human breast tumour specimens. A significant (p = 0.05) correlation was found between the grade of the human breast cancer and similarity to the mouse mammary tumours. The lower the grade, the greater the similarity. Conclusion: Some human breast cancer specimens, in which MMTV-like env DNA sequences have been identified, were shown to have histological characteristics (morphology) similar to MMTV-associated mouse mammary tumours. These observations are compatible with, but not conclusive of, an association between the presence of MMTV-like env DNA sequences and some human breast cancers.

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

“…These assessments were categorized into MMTV-positive and MMTV-negative breast cancer specimens. This is an extension of our previous studies (28). …”

“…At low magnification MMTV-associated mouse mammary tumors do have different characteristics from human breast cancers; however, in some invasive breast cancers, the similarities can be striking in some breast cancers at a cellular level (28). Wellings (44) observed these similarities ∼30 years ago.…”

Lack of Detection of the Mouse Mammary Tumor-like Virus (MMTV) Env Gene in Iranian Women Breast Cancer using Real Time PCR

“…Lawson et al (2006) reported present of MMTV-like virus env DNA in37.3% of 59 human breast cancer patients. They conclude that some breast cancers not only are positive for MMTV-like env DNA but also have histological similarities to MMTVassociated mammary tumor of mice.…”

“…A virus called MMTV-like virus has about 95% sequence homology to MMTV (Lawson et al, 2006). There is controversial evidence on the probable etiologic role of MMTV-like virus on the development of human breast cancer.…”

Viral Origins of Human Cancer

“…Many studies have shown that this virus is transmitted through breast milk to the offspring, while exogenous virus can infect adults [297,298]. Recently, several studies from different groups have reported the detection of MMTV-like sequences in up to 60% of breast biopsies from women with breast cancer and gynecomastia, a possible premalignant condition [299][300][301][302][303]. However, despite many efforts researchers have not agreed on the origins of these viral sequences.…”