The Ras-related gene ERAS is involved in human and murine breast cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Ras genes are frequently mutated in human tumors, but less so in breast cancer.
• Despite low mutation rates, Ras pathway activation is evident in many breast tumors.

Purpose of the Study:

• To identify novel genes involved in breast cancer progression using Sleeping Beauty transposon mutagenesis in mice.
• To characterize the role of ERAS (Expression Ras) in breast cancer development and malignancy.

Main Methods:

• Sleeping Beauty transposon mutagenesis in mouse mammary tumors.
• Forced expression of ERAS in human mammary cells (non-transformed and tumorigenic).
• Analysis of epithelial-to-mesenchymal transition (EMT), stem cell markers, and xenotransplant experiments.
• Immunohistochemistry, RT-qPCR, and bioinformatics analysis of human breast tumor samples.

Main Results:

• ERAS was identified as a novel gene involved in breast cancer progression and malignancy.
• Forced ERAS expression induced EMT and increased stem cell markers in human mammary cells, mediated by miR-200c downregulation.
• ERAS expression in tumorigenic cells led to larger, less differentiated tumors in vivo.
• Aberrant ERAS expression was found in 8-10% of human breast tumors, associated with distant metastasis and reduced metastasis-free survival.

Conclusions:

• Inappropriate ERAS activation contributes to the development of a subset of breast tumors.
• ERAS may serve as a therapeutic target for ERAS-expressing breast tumors.
• Findings highlight ERAS's role in breast cancer malignancy and metastasis.