Expression of the c-jun, jun-B, ets-2 and liver regeneration factor-1 (LRF-1) genes during promotion and progression of rat liver carcinogenesis in the resistant hepatocyte model.
During promotion in the RH-model, the mRNA expression of c-jun and LRF-1 was 2- to 8-fold elevated in both initiated and uninitiated rats receiving 2-AAF. The increase was more pronounced in male than in female rats, and GH treatment of male rats down-regulated the expression towards the level in females. The level in uninitiated 2-AAF-treated livers was as high as in isolated early nodules. jun-B also showed 3- to 8-fold increased expression, but without sex differences. An increased nuclear transcription of the LRF-1 and jun-B genes but not of c-jun was observed. During progression, LRF-1 and ets-2 showed a 2- to 3-fold higher expression in persistent nodules and hepatocellular carcinomas than in the corresponding surrounding liver tissues, whereas the expression of the jun genes was 3- to 4-fold increased both in lesions and in surrounding livers when compared to age-matched control rats. In conclusion, while the changes during promotion might not be connected with control of early focal growth, the increased levels of LRF-1 and ets-2 in advanced lesions might indicate that these genes could contribute to the growth advantage for persistent nodules during progression.
Liao
D Z
DZ
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
Blanck
A
A
Gustafsson
J A
JA
Hällström
I P
IP
D015073:2-Acetylaminofluorene; D051700:Activating Transcription Factor 3; D000818:Animals; D002273:Carcinogens; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D016758:Genes, jun / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors
D051700:Activating Transcription Factor 3; D002273:Carcinogens; D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494071:Ets2 protein, rat; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C068616:liver regeneration factor 1; D015073:2-Acetylaminofluorene