Expression of the bile acid transport protein during liver development and in hepatoma cells.

The expression of the hepatocyte Na(+)-dependent bile acid transport protein during liver development and in hepatoma cells has been characterized using a monoclonal antibody (mAb 25D-1) which specifically recognizes this 49-kDa carrier system. mAb binding studies demonstrated a greatly reduced concentration of this transport protein on the surface of hepatoma tissue culture (HTC) cells, a result consistent with the greater than 95% reduction in bile acid transport capacity when compared with normal adult hepatocytes. Immunoprecipitation procedures with 25D-1 were utilized to quantitate the presence of this transport protein in HTC cells as well as in adult hepatocytes that had been labeled with [35S]methionine or Na125I. These studies indicate that the 49-kDa transport protein is not expressed either on the surface or in any intracellular compartment in HTC cells. mAb binding to fetal cells (day 17) also indicated a greatly decreased number of transport molecules in the plasma membrane. Total cell content of this carrier protein during the next 7 weeks of liver development, as measured by immunoprecipitation, increased in a linear fashion reaching 92% of the adult level at 4 weeks after birth, which parallels the increase in transport function. These results demonstrate that bile acid transport capacity is directly related to the level of expression of this 49-kDa membrane protein.