Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis
Abstract
Transcription factors with helix-loop-helix (HLH) motif play critical roles in controlling the expression of genes involved in lineage commitment, cell fate determination, proliferation, and tumorigenesis. To examine whether the newly identified HLH protein GCIP/CCNDBP1 modulates cell fate determination and plays a role in hepatocyte growth, proliferation, and hepatocarcinogenesis, we generated transgenic mice with human GCIP gene driven by a liver-specific albumin promoter. We demonstrated that in GCIP transgenic mice, the overall liver growth and regeneration occurred normally after liver injury induced by carbon tetrachloride (CCl4). In the diethylnitrosamine (DEN)-induced mouse hepatocarcinogenesis, we demonstrated that overexpression of GCIP in mouse liver suppressed DEN-induced hepatocarcinogenesis at an early stage of tumor development. The number of hepatic adenomas at 24 weeks was significantly lower or not detected in GCIP transgenic male mice compared to the control mice under the same treatment. Although GCIP has little inhibition on the number of hepatic tumors at later stages (40 weeks), hepatocellular tumors in GCIP transgenic mice are smaller and well-differentiated compared to the poorly differentiated tumors i...Continue Reading
References
Citations
MEK2 is a critical modulating mechanism to down-regulate GCIP stability and function in cancer cells
Related Concepts
Related Feeds
Adenoma, Liver Cell
Liver Cell Adenoma or hepatic adenoma is a rare benign tumor. It is associated with birth control use or pregnancy. Discover the latest research on Liver Cell Adenoma here.
Carcinoma, Hepatocellular
Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.
Cell Fate Specification
Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.
Adrenocortical Carcinoma
Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.