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Role of MMTV integration locus cellular genes in breast cancer
1Department of Gynecology and Obstetrics and Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322-4710, USA. rtekmal@emory.edu
Abstract:
Mouse mammary tumorigenesis as a result of mouse mammary tumor virus (MMTV) integrations has helped to identify a wide variety of interesting genes that play a role in mammary development and tumorigenesis. Several such genes int1/wnt1, wnt3, wnt 10B, int2/fgf3, fgf4, int3/notch and int6 have been shown to be genetically altered in naturally formed mammary tumors as a consequence of MMTV integration. Some of these genes have been well characterised and examined in in vivo breast cancer transgenic models for their potential for tumorigenesis. Overexpression of one or more of these genes have resulted in a striking proliferation of mammary gland epithelium of both female and male transgenic mice. Our own studies have demonstrated overexpression of int5/aromatase in mammary glands of virgin and postlactational females leads to the induction of various preneoplastic and neoplastic changes that are similar to early breast cancer, that may, in turn, increase the risks for developing breast cancer. Therefore, further understanding of these genes should provide new insights to their involvement and mechanism of action in breast cancer.
Insights
Mouse mammary tumor virus (MMTV) integrations reveal key genes in mammary development and cancer. Overexpression of genes like aromatase can lead to preneoplastic changes, increasing breast cancer risk.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Mouse mammary tumor virus (MMTV) integrations have identified genes crucial for mammary gland development and tumorigenesis.
- Genes such as Wnt, FGF, Notch, and aromatase are frequently altered in MMTV-induced mammary tumors.
- These genes play significant roles in both normal mammary development and the progression of breast cancer.
Purpose of the Study:
- To investigate the role of specific genes, identified through MMTV integration studies, in mammary gland development and tumorigenesis.
- To understand the mechanisms by which overexpression of these genes contributes to neoplastic changes.
- To explore the potential of these genes as targets for breast cancer research and therapy.
Main Methods:
- Analysis of gene alterations resulting from MMTV integration in naturally occurring mammary tumors.
- Examination of the effects of gene overexpression in in vivo transgenic mouse models.
- Characterization of preneoplastic and neoplastic changes induced by specific gene overexpression, such as aromatase.
Main Results:
- MMTV integration has identified several key genes (Wnt, FGF, Notch, aromatase) involved in mammary tumorigenesis.
- Overexpression of these genes in transgenic mice leads to significant mammary gland epithelial proliferation.
- Overexpression of int5/aromatase in female mice induced preneoplastic and neoplastic changes resembling early breast cancer.
Conclusions:
- Genes identified through MMTV integration are critical players in mammary development and breast cancer.
- Understanding the function and mechanisms of these genes, particularly aromatase, offers insights into breast cancer etiology.
- Further research into these genes may reveal new therapeutic strategies for breast cancer.