Regulation of mannose 6-phosphate/insulin-like growth factor-II receptors and transforming growth factor beta during liver tumor promotion with phenobarbital

Chronic exposure of rats to the liver tumor promoter phenobarbital (PB) significantly reduces the ability of normal hepatocytes, but not of initiated hepatocytes, to respond to mitogenic stimuli. This reduced proliferative ability of normal hepatocytes was correlated with a marked elevation in hepatic concentration of the potent mitoinhibitory factor, transforming growth factor-β1 (TGF-β1). PB also increased the mannose 6-phosphate/insulin-like growth factor-II (M6PI/GF-II) receptor concentration in hepatocytes, with a concomitant up-regulation in gene expression