Multiple mechanisms are responsible for altered expression of gap junction genes during oncogenesis in rat liver

摘要: Although several abnormalities in gap junction (GJ) structure and/or function have been described neoplasms, the molecular mechanisms responsible for many of alterations remain unknown. The identification a family GJ proteins, termed connexins, prompted this study connexin32 (Cx32), connexin26 (Cx26) and connexin43 (Cx43) expression during rat hepatocarcinogenesis. Using antibody, cDNA cRNA probes, we investigated connexin mRNA protein preneoplastic neoplastic livers. In normal liver, Cx32 is expressed hepatocytes throughout hepatic acinus, Cx26 restricted to periportal hepatocytes, Cx43 by mesothelial cells forming Glisson9s capsule. Most altered foci generated diethylnitrosamine (DEN) initiation either phenobarbital (PB) or 2,3,7,8-dichlorodibenzo-p-dioxin (TCDD) promotion exhibited decreased increased staining. Foci from protocol failed display immunoreactivity. majority PB-promoted foci, immunoreactivity independently changes abundance. Continuous thymidine labeling, following cessation PB promotion, showed that downregulation staining reversible are promoter-dependent growth, but irreversible lesions promoter-independent growth. Hepatic neoplasms rats initiated with DEN promoted TCDD also displayed modified expression. While all 24 studied were deficient punctate staining, cellular localization these proteins was apparent some tumors. Immunoblotting crude tissue extracts revealed disordered immunoreactive bands electrophoretic mobility. These observations show hepatomas may downregulate through primary post-translational modifications. Northern blotting total tumor mRNAs demonstrate consistent abundance Cx32, transcripts. Some tumors steady-state transcripts without observable immunoreactivity, indicating Increased levels found immunostaining always localized nonparenchymal cells. Areas bile duct proliferation cholangiomas whereas, cholangiocarcinomas findings differential induction, represent common modifications our results imply connexins useful markers boundary between progression, fail use mechanism modify