The studies on the biology of normal and malignant pigment cells are to determine the mechanisms by which normal melanocytes are stimulated to proliferate and are transformed into melanoma cells; to devise ways of detecting malignant melanocytes with certainty and to be able to control their growth; to prevent skin cancers in albinos by providing the basis for correcting the genetic defect. The projects are grouped as follows: 1. Identifying the genes that control the proliferation and pigmentation of normal and malignant human melanocytes. Included are the gene for tyrosinase and bFGF and the gene for the MSH receptor. cDNA cloning, DNA transfection and antibodies will be used as tools to reach this goal. 2. Determining the subcellular localization of receptors and of other proteins related to proliferation and malignant transformation by the use of labeled ligands and/or antibodies. The approaches will include immunocytochemistry at light and electron miscroscopic levels, and cell fractionation. 3. Cytogenetic analyses of melanocytes from ordinary nevi, dysplastic and congenital nevi, primary melanomas and metastatic melanomas in order to identify chromosomal aberrations that occur in a nonrandom fashion. These analyses include morphological studies of chromosomes and molecular studies of changes in the sites of informative restriction fragment length polymorphisms (RFLPs). 4. Comparing the frequency of transformation of melanocytes from vitiligo skin and normal skin in vivo and in vitro. Studies in vitro will include both human and murine melanocytes, treated with UVB light, X-rays, chemical carcinogens. 5. Identifying cytokines in normal and malignant melanocytes. 6. Correcting the gene defect in human albino melanocytes. The expression of the transfected tyrosinase gene or tyrosinase-controlling gene sequences or respective cDNAs, derived from cultured normal human melanocytes, will be studied.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA004679-29
Application #
3163181
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1976-12-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
29
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Halaban, R; Tyrrell, L; Longley, J et al. (1993) Pigmentation and proliferation of human melanocytes and the effects of melanocyte-stimulating hormone and ultraviolet B light. Ann N Y Acad Sci 680:290-301
Halaban, R; Fan, B; Ahn, J et al. (1992) Growth factors, receptor kinases, and protein tyrosine phosphatases in normal and malignant melanocytes. J Immunother (1991) 12:154-61
Halaban, R; Funasaka, Y; Lee, P et al. (1991) Fibroblast growth factors in normal and malignant melanocytes. Ann N Y Acad Sci 638:232-43
Halaban, R (1991) Growth factors regulating normal and malignant melanocytes. Cancer Treat Res 54:19-40
Halaban, R (1991) Growth factors and tyrosine protein kinases in normal and malignant melanocytes. Cancer Metastasis Rev 10:129-40
Daniolos, A; Lerner, A B; Lerner, M R (1990) Action of light on frog pigment cells in culture. Pigment Cell Res 3:38-43
Halaban, R; Moellmann, G (1990) Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity. Proc Natl Acad Sci U S A 87:4809-13
Stenn, K S; Link, R; Moellmann, G et al. (1989) Dispase, a neutral protease from Bacillus polymyxa, is a powerful fibronectinase and type IV collagenase. J Invest Dermatol 93:287-90
Kwon, B S; Haq, A K; Wakulchik, M et al. (1989) Isolation, chromosomal mapping, and expression of the mouse tyrosinase gene. J Invest Dermatol 93:589-94
Dotto, G P; Moellmann, G; Ghosh, S et al. (1989) Transformation of murine melanocytes by basic fibroblast growth factor cDNA and oncogenes and selective suppression of the transformed phenotype in a reconstituted cutaneous environment. J Cell Biol 109:3115-28

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