The role of p28GANK in rat oval cells activation and proliferation.
BACKGROUND
Human gankyrin gene product (p28GANK) is a novel oncogenic protein ubiquitously overexpressed in hepatocellular carcinoma and also plays a role in cell cycle progression in normal hepatocytes and liver regeneration. However, little is known about the physiological role of p28GANK in the liver oval cell activation and proliferation. We investigated the possible involvement of p28GANK in oval cell-mediated liver regeneration and cell cycle progression.


METHODS
We examined the different p28GANK expression in 2-acetylaminofuorene/partial heptectomy (2-AAF/PH) rats, as a model of oval cell activation, and PH rats by Western blot and immunohistochemistry. Oval cells isolated from 2-AAF/PH rat model were cultured in our study. p28GANK expression was examined in the oval cells after mitogenic stimulation.


RESULTS
In 2-AAF/PH rats, p28GANK was expressed in the activated oval cells and located in the nucleus. p28GANK protein expression was increased in 2-AFF/PH rats after hepatectomy lasting for 96 h when retinoblastoma maintained hyperphosphorylation status at Ser-795. The isolated oval cells express AFP, OV6, CK19, CD34, CD45, c-kit and albumin. After epidermal growth factor stimulation, p28GANK protein was up-regulated in oval cells from 24 to 72 h, which coincided with increased expression of CyclinD1, CDK4 and decreased of Rb protein.


CONCLUSIONS
p28GANK expression was increased in oval cell-mediated liver regeneration and oval cells after mitogenic stimulation. Thus, p28GANK may play a role in oval cell-mediated liver regeneration and liver oval cell cycle progression.
Shan
Yun-Feng
YF
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai, China.
Zhou
Wei-Ping
WP
Fu
Xiao-Yong
XY
Yan
He-Xing
HX
Yang
Wen
W
Liu
Shu-Qin
SQ
Cao
Hui-Fang
HF
Kang
Bin
B
Wu
Meng-Chao
MC
Wang
Hong-Yang
HY
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003135:Common Bile Duct; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006498:Hepatectomy; D008026:Ligation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D017487:Ankyrins; D015415:Biomarkers; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D015073:2-Acetylaminofluorene; D046988:Proteasome Endopeptidase Complex