Cyclin G 1 mediates the poor prognosis of breast cancer through expanding the cancer stem cells

Background: Breast cancer stem cells are a subpopulation of tumor cells with the capacity of self-renew and differentiate into distinct cell types that comprise the bulk of breast cancer. Cyclin G1 has been previously reported as a critical oncogene overexpressed in some cancers. However, the role of cyclin G1 in breast cancer stem cells remains unknown. Methods: The expansion of breast cancer stem cells in cyclin G1 over-expressing cells were assessed by spheroids formation and limited dilution assays. Co-expression of cyclin G1 and CD133/ CD90 was observed in breast cancer cells by real-time PCR. In addition, a tissue microarray was used to examine 135 pairs of breast cancer samples and corresponding adjacent normal mucosae. The expression of cyclin G1 was determined by immunohistochemistry, and further was confirmed by real-time PCR and Western blot. KaplanMeier survival curve was used to determine the correlation of cyclin G1 expression with overall survival of patients. Results: Forced cyclin G1 expression was found remarkably enhanced the expansion of breast cancer stem cells in vitro. Correlated expression of cyclin G1 and tumor stem cell markers was observed in breast cancer. Cyclin G1 expression was detected increased in breast cancer tissue by immunohistochemistry, and further was confirmed at both level of mRNA and protein. Elevated expression of cyclin G1 was highly associated with lower overall survival in breast cancer patients. Compared with non-triple negative breast cancer, high expression of cyclin G1 was found in triple negative breast cancer and played a positive role in chemotherapy resistance. Conclusion: Our findings indicates that cyclin G1 plays an important role in expansion of cancer stem cells and outcome of poor prognosis in breast cancer. Thus, our study reveals a novel biomarker in breast cancer and indicates that cyclin G1 may be a promising therapeutic target for triple negative breast cancer.