Augmentation of butyrate-induced differentiation of human hepatocyte by cyclin E over-expression.
In mammalian cells, cellular differentiation into specific cell types is usually preceded by growth arrest. On the other hand, the induced differentiation may also be preceded by an enhanced G1-S transition of the cell cycle prior to the growth arrest. This suggests that an early increase in proliferation is in some way a prerequisite for subsequent differentiation. We therefore attempted to assess whether we could produce human hepatocytes with further differentiated functions by promoting G1-S transition in a butyrate-treated human hepatocyte cell line. A cyclin E-over-expressing cell line was established by transfecting human cyclin E cDNA. Upon butyrate treatment, the cyclin E-over-expressing cells exhibited a significantly increased albumin-secreting and ammonia-detoxifying capacity when compared to the control cells. In particular, the ornithine transcarbamylase activity was increased in these cells. Collectively, these results implicate that the cyclin E over-expression may augment the hepatocyte-specific functions during the butyrate-induced differentiation process of human hepatocytes by enhancing G1-S cell cycle transition.
Yoon
J-H
JH
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Gwak
G-Y
GY
Woo
G H
GH
Kim
T H
TH
Kim
K-A
KA
Kim
C Y
CY
Lee
H S
HS
D000418:Albumins / Q000378:metabolism; D000641:Ammonia / Q000037:antagonists & inhibitors; D002087:Butyrates / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D019927:Cyclin E / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D009954:Ornithine Carbamoyltransferase / Q000187:drug effects; D010750:Phosphoproteins / Q000032:analysis; D016196:S Phase / Q000187:drug effects; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000032:analysis; D014162:Transfection; D014508:Urea / Q000032:analysis
D000418:Albumins; D002087:Butyrates; D022762:CCAAT-Enhancer-Binding Proteins; D019927:Cyclin E; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D000641:Ammonia; D014508:Urea; D009954:Ornithine Carbamoyltransferase