Zhaozhe Liu, Tao Han

Department of Oncology, General Hospital of ShenyangMilitary Region

Objective:Breast cancer stem cells are a subpopulationof tumor cells with the capacity of self-renew and differentiate into distinctcell types that comprise the bulk of breast cancer. Cyclin G1 has been previouslyreported as a critical oncogene overexpressed in some cancers. However, therole of cyclin G1 in breast cancer stem cells remains unknown. Method: Theexpansion of breast cancer stem cells in cyclin G1 over-expressing cells wereassessed by spheroids formation and limited dilution assays. Co-expression ofcyclin G1 and CD133/CD90 was observed in breast cancer cells by real-time PCRanalysis. In addition, a tissue microarray was used to examine 119 pairs ofbreast cancer samples and corresponding adjacent normal mucosae. The expressionof cyclin G1 was determined by immunohistochemistry, and further was confirmedby real-time PCR and Western blot analysis. Kaplan-Meier survival curve wasused to determine the correlation of cyclin G1 expression with overall survivalof patients. Result: Forced cyclin G1 expression was found remarkablyenhanced the expansion of breast cancer stem cells in vitro. Correlated expressionof cyclin G1 and tumor stem cell markers was also observed in breast cancer.Cyclin G1 expression was detected increased in breast cancer tissue byimmunohistochemistry, and further was confirmed at both level of mRNA and protein.Elevated expression of cyclin G1 was highly associated with lower overallsurvival in breast cancer patients. Compared with non-triple negative breastcancer, high expression of cyclin G1 was found in triple negative breast cancerand played a positive role in chemotherapy resistance. Conclusion: Ourfindings indicates that cyclin G1 plays an important role in expansion ofcancer stem cells and outcome of poor prognosis in breast cancer. Thus, ourstudy reveals a novel biomarker in breast cancer and indicate that cyclin G1may be a promising therapeutic target for triple negative breast cancer patients.

Key Words: Breast cancer  Cancer stem cells  Cyclin G1