Generation of malignant tumor model by heme synthesis failure using mice with Abcb10 deficient

点击翻译按钮获取中文摘要

To investigate how Abcb10 deficiency affect to the accumulation of PPIX and malignant potential of tumor cells, we tried to generate allogeneic tumor transplantation-metastasis models from DEN exposed Abcb10-/-mice. We picked up several cells from liver tumors of Abcb10-/-mice, however could not obtain any tumor cells that acquired spontaneous metastatic potential.We explored in detail the relevance of the physiological role of Abcb10 to the tumorigenesis. Abcb10 deficiency resulted in a defect of heme biosynthesis but did not affect to the stability of Fech. Electron microscopy images of Abcb10-/- hematopoietic cells showed marked iron deposits at the mitochondria. Abcb10F/-; Mx1-Cre mice, with the specific deletion of Abcb10 in hematopoietic cells, showed PPIX accumulation and maturation arrest in reticulocytes.These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia.