CHANGES IN PROTEIN AND MESSENGER-RNA LEVELS OF GROWTH-FACTOR GROWTH-FACTOR RECEPTORS IN RAT LIVERS AFTER ADMINISTRATION OF PHENOBARBITONE OR METHYLCLOFENAPATE

The effects of phenobarbitone and methylclofenapate were studied on th e expression of growth factor and growth factor receptors in livers of male Wistar rats. The major findings were: (1) a significant reductio n in epidermal growth factor receptor (EGFR) protein observed with bot h treatments, and (2) levels of EGFR transcripts were only slightly de creased with both compounds. The reduction in the receptor level there fore does not occur via regulation of transcription. Mannose-6-phospha te receptors (M6PR, also called insulin-like growth factor II receptor ) and M6PR transcripts remained unchanged in both experimental groups. Hepatocyte growth factor receptor (HGFR) transcripts were also unchan ged in both experimental groups. Transcript levels of transforming gro wth factor-beta 1 (TGF-beta 1) were lower in both treatment groups com pared with the control; the reduction was significant in the methylclo fenapate group. This may have relevance to the finding by others that nafenopin, another peroxisome proliferator, suppresses rat hepatocyte apoptosis. Another finding of general interest was that the three ''ho usekeeping genes'', namely albumin, actin and glyceraldehyde-3-phospha te dehydrogenase, were influenced by both treatments thus limiting the ir use as controls for gel loading. The adaptation of a growth regulat ory mechanism via EGFR and its ligands may provide conditions such tha t cells with aberrant growth control have a selective growth advantage over normal cells thus promoting tumorigenesis.