Abstract:
Mouse mammary tumor virus (MMTV) is an established cause of mammary
tumors in mice but its role in human breast cancer is still controversial. MMTV has
been detected in human breast cancer samples in several parts of the world, but the
establishment of a causal role is under debate. Several groups have reported presence
of MMTV-like sequences in human breast cancer. We have also identified MMTV like sequences in 26% of breast cancer tissues from Pakistani population. Here we
propose that integration site analysis of MMTV might help in establishing its role in
breast cancer development. We have used LM-PCR to identify integration sites of
MMTV. Human DNA from Breast cancer samples was digested and ligated to linkers.
An MMTV specific and a linker specific primer were used to amplify integration site.
Amplified DNA was isolated by shotgun cloning in bacteria. Identification of thirteen
distinct integration sites supports the idea of a viral etiology of breast cancer.
Furthermore, our data also indicates anomalous behavior of MMTV-like sequences.
Previous data suggests a totally random integration of MMTV in both mouse and
human genome in cell lines. However we have identified 5 identical integration sites
in eight different breast cancer tissue samples. One particular site at locus 3q26.2 was
identified from 7 samples. This data also supports sequence specific integration of
MMTV. This study is first of its kind in MMTV research. Although, the link is still
not clear, but further studies on these integration sites might reveal a link between
MMTV-like sequences and human breast cancer.
