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.
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.
We did not find any exogenous MMTV env gene sequences in the 50 DNA samples of human breast cancer tissue nor in 22 breast cancer cell lines including MCF-7, which has previously been described as a positive control.
Using the results from the first laboratory and similar studies from the literature, detection of the MMTV-like env gene sequence showed an important geographic pattern with a significantly higher percentage of positive patients with breast carcinoma in Tunisia (74%) compared with patients with breast carcinoma in the United States (36%), Italy (38%), Australia (42%), Argentina (31%), and Vietnam (0.8%)
These data suggest the potential to use HERVs env genes as a diagnosis marker for primary breast cancer, and further studies are needed to identify the mechanism and physiological significance of the reduction of HERV env gene expression during chemotherapy.
Therefore, we amplified and sequenced the full-length RNA of the env gene of the type 1 and 2 HERV-K (HML-2) viruses collected from the plasma of seven HIV-1-infected patients over a period of 1 to 3 years and from five breast cancer patients in order to reconstruct the genetic evolution of these viruses.
Sequences highly similar (>95%) to the mouse mammary tumor virus (MMTV) env gene have been amplified from human DNA samples, including DNA samples from patients with breast cancer (BC) and persons who did not have BC.
Recently, DNA sequences homologous or closely related to MMTV env gene have been specifically detected in breast cancer tissue from significant numbers of American, Australian, and Tunisian women, suggesting a viral etiology for at least a part of human breast cancer.
Oncogenic transformation assays using mouse and rat fibroblasts have localized the transforming activity to the Env proteins encoded by these viruses, which require the putative lung and breast cancer tumor suppressor hyaluronidase 2 (Hyal2) to promote virus entry into cells.
Elevated expression of the tumor suppressing protein p53 is associated with the presence of mouse mammary tumor-like env gene sequences (MMTV-like) in human breast cancer.
Ecotropic virus, which normally does not infect human cells, when pseudotyped with the modified envelope protein now crosses species to infect human breast cancer cell lines that overexpress HER-2 (human epidermal growth factor receptor; also called ERBB2) and HER-4 (also called ERBB4), while human breast cancer cell lines expressing low levels of these receptors remain resistant to infection.
Because the presence of MMTV-like sequences in BC has been associated with laminin receptor expression, a marker of poor prognosis, gestational BCs were analyzed for MMTV env gene-like sequences to explore whether MMTV-like sequences were also associated with its adverse outcome.