Abstract

A number of experimental animal cancers and human cancers have been shown to have high levels of one or both of two intracellular binding proteins which bind vitamin A alcohol (retinol) and vitamin A acid (retinoic acid). The levels are considerably higher than observed for the grossly normal tissue adjacent to the tumors. This elevation in level appears to be a tumor marker in some systems. Consequently, this project plans to use immunocytochemical localization of these proteins to detect tumor foci during carcinogenesis in several well defined rat systems. Antibodies to these proteins isolated from human tissue will be produced and the techniques will then be extended to human tissue and cancers with the goal of being able to identify tumor foci as well as suggest candidates for retinoid therapy. Further, target cell uptake of retinol from the blood transport protein RBP requires a specific plasma membrane receptor. The uptake process will be studied in cells in culture using purified RBP and [3H]retinol. The RBP-receptor interaction will be examined in vitro with membrane preparations and solubilized receptor. Possible interactions with cellular retinol binding protein (CRBP) will be examined. Attempts will be made to purify the receptor and to compare its presence/function in normal and neoplastic tissue.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA020850-09
Application #
3165415
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1977-04-01
Project End
1988-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Maden, M; Ong, D E; Chytil, F (1990) Retinoid-binding protein distribution in the developing mammalian nervous system. Development 109:75-80
MacDonald, P N; Bok, D; Ong, D E (1990) Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human. Proc Natl Acad Sci U S A 87:4265-9
Maden, M; Ong, D E; Summerbell, D et al. (1989) Cellular retinoic acid-binding protein and the role of retinoic acid in the development of the chick embryo. Dev Biol 135:124-32
Shingleton, J L; Skinner, M K; Ong, D E (1989) Characteristics of retinol accumulation from serum retinol-binding protein by cultured Sertoli cells. Biochemistry 28:9641-7
Ong, D E; MacDonald, P N; Gubitosi, A M (1988) Esterification of retinol in rat liver. Possible participation by cellular retinol-binding protein and cellular retinol-binding protein II. J Biol Chem 263:5789-96
Ong, D E; Chytil, F (1988) Presence of novel retinoic acid-binding proteins in the lumen of rat epididymis. Arch Biochem Biophys 267:474-8
Ong, D E; Amedee-Manesme, O (1987) Liver levels of vitamin A and cellular retinol-binding protein for patients with biliary atresia. Hepatology 7:253-6
Chytil, F; Ong, D E (1987) Intracellular vitamin A--binding proteins. Annu Rev Nutr 7:321-35
Ong, D E; Kakkad, B; MacDonald, P N (1987) Acyl-CoA-independent esterification of retinol bound to cellular retinol-binding protein (type II) by microsomes from rat small intestine. J Biol Chem 262:2729-36
MacDonald, P N; Ong, D E (1987) Binding specificities of cellular retinol-binding protein and cellular retinol-binding protein, type II. J Biol Chem 262:10550-6

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