Regulation of selection of liver nodules initiated with N-nitrosodiethylamine and promoted with nodularin injections in Fischer 344 male rats by reciprocal expression of transforming growth factor-β1 and its receptors
✍ Scribed by In Kyoung Lim; Sang Chul Park; Kye Yong Song; Tae Jun Park; Myung Soog Lee; Seong-Jin Kim; Byung Hwa Hyun
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 374 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
To investigate how glutathione-S-transferase placental form (GST-P) hyperplastic nodules (HNs) are selected and to determine the driving force for progression or regression of HNs, changes in transforming growth factor-b1 (TGF-b) and its receptors were examined during hepatocarcinogenesis initiated by N-nitrosodiethylamine (DEN) and promoted by nodularin. The induction of TGF-b1 expression in the GST-P HNs was dependent on nodularin injections for 10 wk, which started the third week after DEN initiation. The kinetics of TGF-b1 induction during carcinogenesis were quite different from that of simple regeneration after partial hepatectomy (PH): hepatocytes initiated with DEN alone induced TGF-b1 expression for 24 d, and subsequent stimulation by PH on the fourteenth day after DEN initiation super-induced TGF-b1 mRNA (50 times that of the control level), as opposed to a transient expression for less than 5 d by PH alone. GST-P HNs did not express TGF-b receptors I (RI) and II (RII) during the early stage of carcinogenesis, whereas the surrounding hepatocytes strongly expressed both of these receptors. On cessation of nodularin injection, however, the expression of RI and RII in the HNs changed signi®cantly: RII nodules appeared, and the number and area of RII/À nodules were signi®cantly increased at 10 wk after the cessation. These ®ndings indicate that induction of TGF-b expression in GST-P HNs might be a strong selection pressure that allows outgrowth of RIIÀ nodules during liver carcinogenesis.