Loss of a putative novel growth inhibitory apoptotic 14 kD polypeptide during progression of rat liver carcinogenesis.

ABSTRACT

Carcinogenesis is a multistep process involving different stages. However, the biological and biochemical factors responsible for the stepwise transition of cells from one stage to the other remains as important enigmas even today. We have recently isolated a putative novel growth inhibitory apoptotic 14 kD polypeptide from normal rat liver. In order to understand the possible functional relationship between 14 kD polypeptide and liver carcinogenesis, the sequential expression of this polypeptide as a function of tumor progression was studied in the rat liver using diethylnitrosamine (DEN) as a carcinogen. Immunoperoxidase and immunoblotting experiments using polyclonal rabbit antisera revealed a gradual reduction in the levels of this polypeptide with tumor progression. No reduction in the levels of this polypeptide was observed in regenerating rat liver after partial hepatectomy. The findings suggest that the loss or reduction of 14 kD polypeptide is linked selectively to abnormal cell proliferation and appears to be a biologically relevant risk factor for the progression of hepatocarcinogenesis in rats.