Related Experiment Video
Updated: Jul 1, 2025

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a
Wenqing Bu1, Xue Sun1, Xiaotong Xue1
1The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Suzhou Medical College, Suzhou, Jiangsu, China.
Background And Aims:
RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a result, the role of RAD51 in liver development and function is unknown. Our aim was to characterize the function of RAD51 in postnatal liver development.
Approach And Results:
RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in chronic liver diseases. We generated a hepatocyte-specific Rad51 deletion mouse model using Alb -Cre ( Rad51 -conditional knockout (CKO)) and Adeno-associated virus 8-thyroxine-binding globulin-cyclization recombination enzyme to evaluate the function of RAD51 in liver development and regeneration. The phenotype in Rad51 -CKO mice is dependent on CRE dosage, with Rad51fl/fl ; Alb -Cre +/+ manifesting a more severe phenotype than the Rad51fl/fl ; Alb -Cre +/- mice. RAD51 deletion in postnatal hepatocytes results in aborted mitosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51fl/fl ; Alb -Cre +/+ mice. While liver regeneration is compromised in Rad51 -CKO mice, they are more tolerant of carbon tetrachloride-induced hepatic injury and resistant to diethylnitrosamine/carbon tetrachloride-induced HCC. A chronic inflammatory microenvironment created by the senescent hepatocytes appears to activate ductular reaction the transdifferentiation of cholangiocytes to hepatocytes. The newly derived RAD51 functional immature hepatocytes proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC.
Conclusions:
Our results demonstrate a novel function of RAD51 in liver development, homeostasis, and tumorigenesis. The Rad51 -CKO mice represent a unique genetic model for premature liver senescence, fibrosis, and hepatocellular carcinogenesis.
Related Concept Videos
Abnormal Proliferation
DNA Damage can Stall the Cell Cycle
Replicative Cell Senescence
The Ras Gene
Ras is a...
Negative Regulator Molecules
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

