Abstract

Our objective is to elucidate the mechanisms that regulate gene expression in mammalian cells, particularly mechanisms that regulate alpha-fetoprotein (AFP) gene transcription during ontogenesis and hepatocarcinogenesis. We determined that differentiation and hepatocarcinogenesis involved a change in the transcriptional activity of the AFP gene. We plan to examine further the relationship of chromatin structure and DNA methylation to AFP gene activity. We identified hepatoma-associated nonhistone proteins in AFP-producing hepatomas. We will continue to identify nuclear proteins that affect AFP gene hepatomas. We will develop an in vitro transcription system to examine how nuclear proteins, hormone receptors, and carcinogens affect AFP gene transcription. (M)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025098-11
Application #
3166698
Study Section
Pathology B Study Section (PTHB)
Project Start
1978-07-01
Project End
1989-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405

  Publications

Chen, H; Dong, J M; Liu, Y et al. (1999) Identification of a cis-acting element in the rat alpha-fetoprotein gene and its specific binding proteins in F9 cells during retinoic acid-induced differentiation. J Cell Biochem 72:25-34
Liu, Y; Chen, H; Chiu, J F (1994) Identification of a retinoic acid response element upstream of the rat alpha-fetoprotein gene. Mol Cell Endocrinol 103:149-56
Fukuda, K; Kojiro, M; Chiu, J F (1994) Differential regulation of tissue transglutaminase in rat hepatoma cell lines McA-RH7777 and McA-RH8994: relation to growth rate and cell death. J Cell Biochem 54:67-77
Liu, Y; Chiu, J F (1994) Transactivation and repression of the alpha-fetoprotein gene promoter by retinoid X receptor and chicken ovalbumin upstream promoter transcription factor. Nucleic Acids Res 22:1079-86
Liu, Y; Chen, H; Dong, J M et al. (1994) cis-acting elements in 5'-flanking region of rat alpha-fetoprotein mediating retinoic acid responsiveness. Biochem Biophys Res Commun 205:700-5
Fukuda, K; Kojiro, M; Chiu, J F (1993) Cross-linked cytokeratin polypeptides in liver and hepatoma cells: possible association with the process of cell degeneration and death. Hepatology 17:118-24
Fukuda, K; Kojiro, M; Chiu, J F (1993) Demonstration of extensive chromatin cleavage in transplanted Morris hepatoma 7777 tissue: apoptosis or necrosis? Am J Pathol 142:935-46
Zhang, X K; Egan, J O; Huang, D et al. (1992) Hepatitis B virus DNA integration and expression of an erb B-like gene in human hepatocellular carcinoma. Biochem Biophys Res Commun 188:344-51
Zhang, X K; Dong, J M; Chiu, J F (1991) Regulation of alpha-fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping binding site. J Biol Chem 266:8248-54
Zhang, X K; Zucker, M L; Huang, D P et al. (1991) Alteration of cellular oncogene expression in L1210 cells by a nitrosourea analog of thymidine. Cancer Commun 3:119-26

Showing the most recent 10 out of 28 publications