© 1996 Oxford University Press
research-article |
CANCER BIOLOGY: Expression of transforming growth factor alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met and acidic fibroblast growth factor/fibroblast growth factor receptors during hepatocarcinogenesis
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health 37 Convent Drive, Bethesda, MD 20892-4255, USA
1To whom correspondence should be addressed
It is widely believed that abnormal production of poly-peptide growth factors, together with other molecular alterations, play an important role in neoplastic development Transforming growth factor alpha (TGF
), hepato-cyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth factors that contribute to liver regeneration occurring via both hepato-cyte replication and oval cell proliferation. It is not clear, however, whether and to what extent these growth factors are also involved in hepatocarcinogenesis. In the present study, the gene expression of TGF, HGF and aFGF and their corresponding receptors was examined by Northern blotting and in situ hybridization during hepatocarcinogenesis induced by the Solt-Farber protocol. All three growth factor/receptor systems, TGF/epidermal growth factor receptor (EGFR), HGF/c-met and aFGF/FGF receptors (flg and bek) were significantly elevated at early time points when oval cells were proliferating. Their respective expression decreased after 1 month and remained at a low level until the development of liver tumors. In all hepatocellular carcinomas (HCC) examined, the transcripts of TGF and aFGF were highly expressed, while those of HGF were low. With regard to the receptor expression in the tumors, EGFR was present at varying levels, c-met was expressed at higher levels and flg increased significantly, whereas bek remained at low levels. These data suggest that TGF and aFGF are the major growth factors involved in the progression of HCC, and that the signal of aFGF is mainly transduced by the receptor flg in HCC. Furthermore, HCC cells were phenotypically very similar to oval cells with regard to the gene expression of growth factor/ receptor systems. These results, along with the finding that all the HCC cells are positive for the oval cell antigen OV6, and that cytokeratin 19 is heavily expressed in both tumor and oval cells, strongly suggest that at least some of the HCC induced by the Solt-Farber protocol may be derived from oval cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Zheng, S.-h. Oh, Y. Jung, and B. E. Petersen Oval Cell Response in 2-Acetylaminofluorene/Partial Hepatectomy Rat Is Attenuated by Short Interfering RNA Targeted to Stromal Cell-Derived Factor-1 Am. J. Pathol., December 1, 2006; 169(6): 2066 - 2074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Lasagna, O. Fantappie, M. Solazzo, L. Morbidelli, S. Marchetti, G. Cipriani, M. Ziche, and R. Mazzanti Hepatocyte growth factor and inducible nitric oxide synthase are involved in multidrug resistance-induced angiogenesis in hepatocellular carcinoma cell lines. Cancer Res., March 1, 2006; 66(5): 2673 - 2682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Huang, C. Yu, C. Jin, M. Kobayashi, C. A. Bowles, F. Wang, and W. L. McKeehan Ectopic Activity of Fibroblast Growth Factor Receptor 1 in Hepatocytes Accelerates Hepatocarcinogenesis by Driving Proliferation and Vascular Endothelial Growth Factor-Induced Angiogenesis Cancer Res., February 1, 2006; 66(3): 1481 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K N Lowes, E J Croager, L J Abraham, J K Olynyk, and G C T Yeoh Upregulation of lymphotoxin {beta} expression in liver progenitor (oval) cells in chronic hepatitis C Gut, September 1, 2003; 52(9): 1327 - 1332. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. A. Diwan, G. Ramakrishna, L. M. Anderson, and D. Ramljak Overexpression of Grb2 in Inflammatory Lesions and Preneoplastic Foci and Tumors Induced by N-Nitrosodimethylamine in Helicobacter hepaticus--Infected and -Noninfected A/J Mice Toxicol Pathol, July 1, 2000; 28(4): 548 - 554. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Gariboldi, R. Pascale, G. Manenti, M. R.D. Miglio, D. Calvisi, A. Carru, T. A. Dragani, and F. Feo Analysis of loss of heterozygosity in neoplastic nodules induced by diethylnitrosamine in the resistant BFF1 rat strain Carcinogenesis, July 1, 1999; 20(7): 1363 - 1368. [Abstract] [Full Text] [PDF]
|
|