Mammary tumor induction in transgenic mice expressing an RNA-binding protein

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• The c-myc mRNA coding region instability determinant binding protein (CRD-BP) is a multifunctional RNA-binding protein.
• CRD-BP expression is typically high during fetal development and low in normal adult tissues.
• Reactivated CRD-BP expression is observed in human breast, colon, and lung tumors, suggesting a role in tumorigenesis.

Purpose of the Study:

• To investigate the role of CRD-BP as a proto-oncogene in mammary neoplasia.
• To establish a transgenic mouse model for studying CRD-BP-induced mammary tumors.

Main Methods:

• Expression of CRD-BP in mammary epithelial cells of adult transgenic mice using the whey acidic protein (WAP) promoter.
• Analysis of mammary tumor incidence, metastasis, and gene expression in WAP-CRD-BP mice compared to nontransgenic controls.

Main Results:

• High incidence of mammary tumors (95% and 60%) in WAP-CRD-BP mouse lines with varying CRD-BP expression levels.
• Tumors in WAP-CRD-BP mice exhibited metastasis.
• Upregulation of H19 RNA and insulin-like growth factor II mRNA in non-neoplastic mammary tissue of WAP-CRD-BP mice.

Conclusions:

• CRD-BP expression in adult mammary epithelial cells is sufficient to induce mammary tumors in mice.
• WAP-CRD-BP mice represent a novel model for studying mammary neoplasia and human breast cancer.
• The findings support the hypothesis that CRD-BP is a proto-oncogene.