Effects And Mechanisms Of New ER Co-regulatory Factor On Breast Cancer

Breast cancer is one of the common malignant tumors that threaten women’shealth. Estrogen signaling pathway plays an important role in the development andprogression of breast cancer. Estrogen receptors (ERs) mediate the effects ofestradiol (E2) through genomic and nongenomic mechanisms. The signalingregulation between ER pathway and other pathways is intimate, as ERs not onlytrigger classical genomic mechanism of estradiol action but also exert through a rapidtransduction way to regulate gene transcription and cell proliferation by itsnongenomic mechanism. Dysregulation of ER signaling pathway is correlated withtumor aggravation, metastasis and resistance to the endocrine therapy. In fact, thebiological effects of ERs result from their interaction with co-regulators. Therefore, itis of great significance to discover and study new co-regulators for elucidating ERsignaling pathway, clarifing the mechanisms of breast cancer, searching fortherapeutic methods and developing new drugs.In this study, we found the GA5interacted with estrogen receptor, and the GA5is a co-regulation factor of the estrogen signaling pathway. We identified that the GA5interacted with DBD domain of ERα and ERβ by immunoprecipitation, and ERβinteracted with the GA5Δcoil-coil. To research GA5biological function further, wefound the GA5interacted with SUMO related enzymes using the yeast two-hybridexperiments. This study found the GA5could be decorated by SUMO, The GA5thatfailed to enhance SUMO of ERβK4R could enhance the SUMO of ERβ. Furtherresearch showed that the GA5Δcoil-coil couldn’t enhance the SUMO of ERβ. GA5could specifically decrease the transcriptional activity of ERβ. Half-life experimentsillustrated GA5could stabilize the protein levels of ERβ. Real-time PCRdemonstrated the GA5regulated the ERβ downstream gene P21and PRb. GA5waspositioned in nuclear spots sequences, which was caused by the GA5(1-147). Growthcurve demonstrated GA5could suppress HepG2and ZR751cells growth. The FCMillustrated GA5blocked cells in the G0G1phase.In conclusion, as a co-regulator of ERβ, GA5interacts with ERβ and plays animportant function in the signal path, Therefore, further study on the function and mechanisms of GA5in ER signal pathway may provide better clinical therapy ofbreast cancer and prognosis assessment, beneficial thread, and new molecular targetsfor research on cancer development.