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.
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.
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.
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.
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.
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.
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.
We have detected by PCR a 660-bp sequence similar to the env gene of MMTV but not to the known endogenous viruses, in 38% of human breast cancers examined (Wang et al., Cancer Res., 55: 5173-5179, 1995).
We have reported previously that a 660-bp sequence homologous to the env gene of the mouse mammary tumor virus, but not to the known endogenous retroviruses, was present in 38% of human breast cancers (Y. Wang et al., Cancer Res., 55: 5173-5179, 1995).
We previously reported that a 660-bp sequence that is homologous to the env gene of the mouse mammary tumor virus (MMTV) but not to endogenous retroviruses or to other known genes was present in 38% of human breast cancers and in some breast cancer cell lines studied (Y. Wang et al., Cancer Res., 55: 5173-5179, 1995).
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.