MMTV mouse models and the diagnostic values of MMTV-like sequences in human breast cancer

Abstract

Mouse mammary tumor virus (MMTV) long terminal repeat (LTR)-driven transgenic mice are excellent models for breast cancer as they allow for the targeted expression of various oncogenes and growth factors in neoplastic transformation of mammary glands. Numerous MMTV-LTR-driven transgenic mouse models of breast cancer have been created in the past three decades, including MMTV-neu/ErbB2, cyclin D1, cyclin E, Ras, Myc, int-1 and c-rel. These transgenic mice develop mammary tumors with different latency, histology and invasiveness, reflecting the oncogenic pathways activated by the transgene. Recently, homologous sequences of the env gene of MMTV have been identified in approximately 40% of human breast cancers, but not in normal breast or other types of cancers, suggesting possible involvement of mammary tumor virus in human breast carcinogenesis. Accumulating evidence demonstrates the association of MMTV provirus with progesterone receptor, p53 mutations and advanced-stage breast cancer. Thus, the detection of MMTV-like sequences may have diagnostic value to predict the clinical outcome of breast cancer patients.

Keywords::

• breast cancer
• c-rel
• cyclin D1
• cyclin E
• HMTV
• int-1
• mouse mammary tumor virus
• Myc
• neu/ErbB2/HER2
• p53
• prognosis
• Ras
• transgenic mouse

Acknowledgements

We thank Elizabeth Fry for technical assistance.

Financial & competing interests disclosure

Kazushi Inoue has been supported by NIH/NCI 5R01CA106314, American Cancer Society RSG-07-207-01-MGO and Wake Forest University Golfers against Cancer grant P30CA12197GAC. Pankaj Taneja is currently supported by the Susan G Komen Foundation postdoctoral fellowship KG080179. Donna P Frazier was supported by the Ruth L Kirschstein National Research Service Award Institutional Research Training Grant (5T32CA079448, F. Torti) from the NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.