title: Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice.
abstract: Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional coactivator, plays an important role in regulation of cell apoptosis in chemoresistant cancer cells. However, its role in radiation-induced apoptosis in hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC-3(-/-)) mice to assess the role of SRC-3 in radiation-induced hematopoietic injury in vivo. After a range of doses of irradiation, SRC-3(-/-) mice exhibited lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and excessive BM depression, which resulted in a significantly higher mortality compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3(-/-) mice showed a remarkable increase in radiation-induced apoptosis. Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the radiosensitivity of hematopoietic cells, which highlights a potential therapeutic target for radiation-induced hematopoietic injury.
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Shilei
authors.initials: S
authors.lastname: Chen
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.forename: Xinze
authors.initials: X
authors.lastname: Ran
authors.forename: Yongping
authors.initials: Y
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism*; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology*; D011836:Radiation Tolerance; D014916:Whole-Body Irradiation
chemical_list: C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3
keywords: Radiosensitivity; SRC-3; apoptosis; hematopoiesis; knockout mice