Carcinogenesis, Vol. 23, No. 3, 435-445,
March 2002
© 2002 Oxford University Press
CARCINOGENESIS |
Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma
Department of Biochemistry, The University of Western Australia, Crawley, 6009, Australia
Oval cells are bipotential liver stem cells able to differentiate into hepatocytes and bile duct epithelia. In normal adult liver oval cells are quiescent, existing in low numbers around the periportal region, and proliferate following severe, prolonged liver trauma. There is evidence implicating oval cells in the development of hepatocellular carcinoma, and hence the availability of an immortalized oval cell line would be invaluable for the study of liver cell lineage differentiation and carcinogenesis. A novel approach in the generation of cell lines is the use of the p53 knockout mouse. Absence of p53 allows a cell to cycle past the normal Hayflick limit, rendering it immortalized, although subsequent genetic alterations are thought necessary for transformation. p53 knockout mice were fed a choline-deficient, ethionine-supplemented diet, previously shown to increase oval cell numbers in wild-type mice. The oval cells were isolated by centrifugal elutriation and maintained in culture. Colonies of hepatic cells were isolated and characterized with respect to phenotype, growth characteristics and tumorigenicity. Analysis of gene expression by Northern blotting and immunocytochemistry suggests they are oval-like cells by virtue of albumin and transferrin expression, as well as the oval cell markers alpha fetoprotein, M2-pyruvate kinase and A6. Injection into athymic nude mice shows the cell lines are capable of forming tumors which phenotypically resemble hepatocellular carcinoma. Thus, the use of p53 null hepatic cells successfully generated immortalized and tumorigenic hepatic stem cell lines. The results presented support the idea that deleting p53 allows immortalization and contributes to the transformation of the oval-like cell lines. Further, the tumorigenic status of the cell lines is direct evidence for the participation of oval cells in the formation of hepatocellular carcinoma.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Okabe, Y. Tsukahara, M. Tanaka, K. Suzuki, S. Saito, Y. Kamiya, T. Tsujimura, K. Nakamura, and A. Miyajima Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver Development, June 1, 2009; 136(11): 1951 - 1960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Lau, Z. F. Yang, D. W. Ho, M. N. Ng, G. C.T. Yeoh, R. T.P. Poon, and S. T. Fan An Akt/Hypoxia-Inducible Factor-1{alpha}/Platelet-Derived Growth Factor-BB Autocrine Loop Mediates Hypoxia-Induced Chemoresistance in Liver Cancer Cells and Tumorigenic Hepatic Progenitor Cells Clin. Cancer Res., May 15, 2009; 15(10): 3462 - 3471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Jellicoe, S. J. Nichols, B. A. Callus, M. V. Baker, P. J. Barnard, S. J. Berners-Price, J. Whelan, G. C. Yeoh, and A. Filipovska Bioenergetic differences selectively sensitize tumorigenic liver progenitor cells to a new gold(I) compound Carcinogenesis, June 1, 2008; 29(6): 1124 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Davies, B. Knight, Y. W. Tian, G. C.T. Yeoh, and J. K. Olynyk Hepatic oval cell response to the choline-deficient, ethionine supplemented model of murine liver injury is attenuated by the administration of a cyclo-oxygenase 2 inhibitor Carcinogenesis, August 1, 2006; 27(8): 1607 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Knight, B. B. Yeap, G. C. Yeoh, and J. K. Olynyk Inhibition of adult liver progenitor (oval) cell growth and viability by an agonist of the peroxisome proliferator activated receptor (PPAR) family member {gamma}, but not {alpha} or {delta} Carcinogenesis, October 1, 2005; 26(10): 1782 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. ZENDER, W. XUE, C. CORDON-CARDO, G.J. HANNON, R. LUCITO, S. POWERS, P. FLEMMING, M.S. SPECTOR, and S.W. LOWE Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 251 - 261. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Vondracek, M. Machala, V. Bryja, K. Chramostova, P. Krcmar, C. Dietrich, A. Hampl, and A. Kozubik Aryl Hydrocarbon Receptor-Activating Polychlorinated Biphenyls and Their Hydroxylated Metabolites Induce Cell Proliferation in Contact-Inhibited Rat Liver Epithelial Cells Toxicol. Sci., January 1, 2005; 83(1): 53 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tan, P. G. Besant, X. L. Zu, C. W. Turck, M. A. Bogoyevitch, S. G. Lim, P. V. Attwood, and G. C. Yeoh Histone H4 histidine kinase displays the expression pattern of a liver oncodevelopmental marker Carcinogenesis, November 1, 2004; 25(11): 2083 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Ishikawa, K Nakao, K Matsumoto, D Nishimura, T Ichikawa, K Hamasaki, and K Eguchi Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma Gut, June 1, 2004; 53(6): 884 - 889. [Abstract] [Full Text] [PDF]
|
|