Deletion of Bid impedes cell proliferation and hepatic carcinogenesis.
Mechanisms that control the proliferation capability of the initiated cells during hepatocarcinogenesis are still largely unclear. We investigated the role of a pro-death Bcl-2 family protein, Bid, in liver tumor development using a neonatal diethylnitrosamine model. Diethylnitrosamine was administrated to 15-day-old wild-type and bid-null mice. The development of microfoci at the early stage and of gross tumors at the later stage was compared between the two groups of mice. Both microfoci and gross tumor development were significantly retarded in the bid-null mice, despite reduced cell death as measured by TUNEL staining. Further studies indicated that there were significantly less proliferating cells in diethylnitrosamine-treated bid-null livers. The regulation of cell proliferation by Bid was confirmed in two other systems not involving carcinogenesis. Hepatocyte proliferation following partial hepatectomy and T lymphocyte proliferation following anti-CD3 stimulation were both retarded in bid-null mice. Thus, these studies revealed a previously undisclosed function of Bid in regulating cell proliferation, which can be important to tumor development. Furthermore, the role of Bid in promoting hepatocarcinogenesis is in contrast to its reported role in suppressing myeloid leukemia and thus suggests an organ- and/or etiology-specific role of the Bcl-2 family proteins in regulating oncogenesis.
Bai
Li
L
Department of Pathology, University of Pittsburgh School of Medicine, Scaife Hall, 7th Floor, Room S739, 3550 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
Ni
Hong-Min
HM
Chen
Xiaoyun
X
DiFrancesca
Daniell
D
Yin
Xiao-Ming
XM
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D016923:Cell Death; D049109:Cell Proliferation; D004052:Diethylnitrosamine; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D002352:Carrier Proteins; D004052:Diethylnitrosamine