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Mouse mammary tumor virus‐like env sequences in human breast cancer
Author(s) -
Mok Myth T.S.,
Lawson James S.,
Iacopetta Barry J.,
Whitaker Noel J.
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23372
Subject(s) - mouse mammary tumor virus , virus , mammary gland , breast cancer , cancer , virology , biology , human breast , cancer research , medicine , pathology , genetics
Mouse mammary tumor virus (MMTV) has long been known as a causal agent of breast cancer in mice. To date, varied MMTV‐like envelope gene ( env ) sequences have been identified in up to 74% of human breast cancers. However, the role and origin of these MMTV‐like sequences in human breast cancer remain uncertain. Our study was initiated to study the integration of MMTV‐like env sequences in human breast cancer. PCR screening has identified 28 (56%) Australian breast cancer specimens and 7 (87.5%) human breast cancer cell lines to be positive for MMTV‐like env sequence. In the MCF‐7 genome, a fragment containing an MMTV‐like env sequence of ∼1.9 kb plus a downstream rodent‐like sequence of ∼200 bp was found to be integrated into a bacterial‐like β‐lactamase sequence by insertional mutagenesis. The identified MMTV‐rodent fragment is present in some MCF‐7 sublines but absent in the screened specimens and other cell lines. Sporadic mutations found in this fragment indicate it has multiple copies in the MCF‐7 genome. Sequence analysis has identified a novel ORF of ∼1.6 kb which is 94–99% identical to MMTV env genes. RT‐PCR was performed on the MCF‐7 cDNA but no MMTV‐like env transcript was detected. This is the first report to reveal the locus of MMTV‐like env sequence in human cells. The MMTV‐like env sequence was shown to be distinct from the human endogenous retroviral sequences and is closely related to rodents. © 2008 Wiley‐Liss, Inc.