Abstract

Our objective is to determine whether liver fatty acid binding protein (L-FABP) and a closely related protein act as cytoplasmic receptors of growth-promoting fatty acid metabolites and ultimate carcinogens in rat hepatocytes. We have assembled a body of evidence in support of our proposal that L-FABP contains ligands that promote growth in normal, pre- malignant and malignant hepatocytes in rats. In addition, L-FABP is the principal protein target of the liver carcinogen, N-2- acetylaminofluorene (2-acetylaminofluorene), during early stages of carcinogenesis. We will study ligands of liver fatty acid binding protein and a related polypeptide both in vitro and in normal and carcinogen-altered hepatocytes of rats, as follows: Project I: Ligands of L-FABP 1. In vitro dissociable ligands of L-FABP 2. In vivo dissociable ligands of L-FABP 3. Competition between normal ligands and activated carcinogen Project II: Cloning, Ligand-Binding and Cellular Levels of a Protein Related to L-FABP 1. cDNA cloning, nucleotide sequence and identification 2. In vitro dissociable ligands 3. Level of regulation 4. Tissue levels

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA005945-25
Application #
3163216
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1978-12-01
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
25
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Institute for Cancer Research
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19111

  Publications

Sorof, S (1994) Modulation of mitogenesis by liver fatty acid binding protein. Cancer Metastasis Rev 13:317-36
Khan, S H; Sorof, S (1994) Liver fatty acid-binding protein: specific mediator of the mitogenesis induced by two classes of carcinogenic peroxisome proliferators. Proc Natl Acad Sci U S A 91:848-52
Keler, T; Sorof, S (1993) Growth promotion of transfected hepatoma cells by liver fatty acid binding protein. J Cell Physiol 157:33-40
Keler, T; Barker, C S; Sorof, S (1992) Specific growth stimulation by linoleic acid in hepatoma cell lines transfected with the target protein of a liver carcinogen. Proc Natl Acad Sci U S A 89:4830-4
Khan, S H; Sorof, S (1990) Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen. Proc Natl Acad Sci U S A 87:9401-5
Raza, H; Pongubala, J R; Sorof, S (1989) Specific high affinity binding of lipoxygenase metabolites of arachidonic acid by liver fatty acid binding protein. Biochem Biophys Res Commun 161:448-55
Munir, K M; Custer, R P; Sorof, S (1989) Normal hepatocytes exhibiting histone H3 with antibody accessible sites that are cryptic in carcinogen-altered hepatocytes. Cancer Res 49:424-32
Munir, K M; Blackburn, G R; Sorof, S (1988) Late target protein of the carcinogen N-2-fluorenylacetamide in rat liver. Cancer Res 48:6745-52
Bassuk, J A; Tsichlis, P N; Sorof, S (1987) Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes. Proc Natl Acad Sci U S A 84:7547-51
Sorof, S; Custer, R P (1987) Elevated expression and cell cycle deregulation of a mitosis-associated target polypeptide of a carcinogen in hyperplastic and malignant rat hepatocytes. Cancer Res 47:210-20

Showing the most recent 10 out of 14 publications