Open AccessThe gene expression of hepatic proteins responsible for DNA repair and cell proliferation in tamoxifen‐induced hepatocarcinogenesis
Author(s) -
Kasahara Toshihiko,
Kuwayama Chitose,
Hashiba Masamichi,
Harada Tsuyoshi,
Kakinuma Chihaya,
Miyauchi Makoto,
Degawa Masakuni
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01486.x
Subject(s) - proliferating cell nuclear antigen , carcinogenesis , biology , cyclin d1 , dna repair , cell growth , xrcc1 , microbiology and biotechnology , dna damage , cancer research , gene expression , tamoxifen , cyclin d , xeroderma pigmentosum , cell cycle , cell , gene , dna , cancer , biochemistry , genetics , breast cancer , single nucleotide polymorphism , genotype
Altered gene expression of the DNA repair‐ and cell proliferation‐associated proteins/enzymes was examined during the process of tamoxifen‐induced hepatocarcinogenesis in female Sprague‐Dawley rats. When rats were treated by gavage with a single dose of tamoxifen (20 mg/kg body weight) or with the same dose given at 24‐h intervals for 2, 12 or 52 weeks, no histopathological change was observed in the liver after 2 weeks. Pathologically altered cell foci and placental form of glutathione‐S‐transferase (GST‐P)‐positive foci were observed in the liver after 12 weeks of treatment. Treatment for 52 weeks resulted in the formation of liver hyperplastic nodules that strongly expressed GST‐P. During the process of carcinogenesis, changes in hepatic gene expression of DNA repair proteins/enzymes (XPA and XPC, xeroderma pigmentosum complementation groups A and C, respectively; APE, apurinic/apyrimidinic endonuclease) and of cell proliferation‐associated proteins (c‐myc; PCNA, proliferating cell nuclear antigen; cyclin D1, cyclin B, and p34cdc2) were examined by RT‐PCR. The gene expression of XPA and APE was increased by the tamoxifen treatment for 2 or 12 weeks, but no increase was observed after the 52‐week treatment. In addition, no significant change in XPC gene expression occurred at any period examined. The gene expression of c‐myc, PCNA , and cyclin D1 was increased in a time‐dependent fashion up to 12 weeks of treatment, and this increase was maintained up to 52 weeks of treatment. The gene expression of cyclin B and p34cdc2 was increased after the 1‐day treatment, reverted to the control level at 2 and 12 weeks of treatment, and was remarkably increased after the 52‐week treatment. In the present study, we demonstrate the altered gene expression of various proteins/enzymes involved in DNA repair, cell growth and the cell cycle during the process of tamoxifen‐induced hepatocarcinogenesis. We discuss the relationship between the altered gene expression and hepatocarcinogenesis.