TY - JOUR
T1 - Mouse model of hepatocellular hyperplastic nodule formation characterization of mRNA expression
AU - Nagao, Yasuyuki
AU - Wan, Yu-Jui Yvonne
AU - Yuan, Qi X.
AU - Kachi, Kazutomo
AU - Marceau, Norman
AU - French, Samuel W.
PY - 1999/7
Y1 - 1999/7
N2 - In previous studies a mouse model of hepatocellular tumorigenesis was developed. In this model of chronic griseofulvin feeding, preneoplastic foci developed over 5 months and numerous hyperplastic nodules with a few hepatocellular carcinomas developed after 10 months. In a subsequent study where 5- and 16-month livers were tested, the immediate early gene c-fos mRNA and transcription factor AP-1 were activated as well as was NFκB at both time intervals. However, the PPARα and RXRα genes were down-regulated. The evidence indicated that immediate early genes were involved in the promotion of tumor formation and that the direct hyperplasia pathway of regeneration was suppressed. To further characterize the involvement of the immediate early gene expression as well as other genes involved in the preneoplastic process we measured mRNA for c-jun, c-myc, hepatocyte growth factor activator (HGF-A), TGFβRII, γ-glutamyl transpeptidase (GGT), cytokeratin (CK8), ubiquitin (UB) and cellular transglutaminase (TG). The data indicated that c- jun an immediate early gene and c-myc, a delayed early gene were up- regulated at 5 and 16 months of feeding, both when preneoplastic foci appeared and when hyperplastic nodules developed. However, HGF-A was down- regulated at both time intervals. TGFβRII was up-regulated, as was GGT, CK8, TG and UB. GGT up-regulation was the only progression seen in gene expression at 16 months. It is concluded that a complex of cell proliferation and cell maintenance genes are involved in tumorigenesis in the mouse model of tumor promotion.
AB - In previous studies a mouse model of hepatocellular tumorigenesis was developed. In this model of chronic griseofulvin feeding, preneoplastic foci developed over 5 months and numerous hyperplastic nodules with a few hepatocellular carcinomas developed after 10 months. In a subsequent study where 5- and 16-month livers were tested, the immediate early gene c-fos mRNA and transcription factor AP-1 were activated as well as was NFκB at both time intervals. However, the PPARα and RXRα genes were down-regulated. The evidence indicated that immediate early genes were involved in the promotion of tumor formation and that the direct hyperplasia pathway of regeneration was suppressed. To further characterize the involvement of the immediate early gene expression as well as other genes involved in the preneoplastic process we measured mRNA for c-jun, c-myc, hepatocyte growth factor activator (HGF-A), TGFβRII, γ-glutamyl transpeptidase (GGT), cytokeratin (CK8), ubiquitin (UB) and cellular transglutaminase (TG). The data indicated that c- jun an immediate early gene and c-myc, a delayed early gene were up- regulated at 5 and 16 months of feeding, both when preneoplastic foci appeared and when hyperplastic nodules developed. However, HGF-A was down- regulated at both time intervals. TGFβRII was up-regulated, as was GGT, CK8, TG and UB. GGT up-regulation was the only progression seen in gene expression at 16 months. It is concluded that a complex of cell proliferation and cell maintenance genes are involved in tumorigenesis in the mouse model of tumor promotion.
KW - γ-Glutamyl transpeptidase
KW - c-Jun
KW - c-Myc
KW - CK8
KW - Griseofulvin
KW - Hepatocellular carcinoma
KW - Hepatocellular neoplasia
KW - Hepatocyte growth factor
KW - Preneoplasia
KW - TGTβRII
KW - Transglutaminase
KW - Ubiquitin
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U2 - 10.1016/S1386-6346(99)00022-4
DO - 10.1016/S1386-6346(99)00022-4
M3 - Article
AN - SCOPUS:0032816783
VL - 15
SP - 110
EP - 123
JO - International Hepatology Communications
JF - International Hepatology Communications
SN - 0928-4346
IS - 2
ER -