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.
Bibliographical noteFunding Information:
We wish to thank Dr. R. Taub from University of Pennsylvania School of Medicine and Dr. T.S. Papas from the National Cancer Institute, Maryland, for kindly providing the rat LRF-1 cDNA clone and mouse ets-2 cDNA clone, respectively. We also wish to thank Dr. L.C. Eriksson for his expertise in classifying the liver lesions. This work was supported by the NIEHS, NIH (1ROl CA57 925-02), the Swedish Cancer Society and Swedish Society for Medical Research.
- Growth control
- Liver neoplasms
- Sex differentiation
- Transcription factors