In this research, gene transfer methods will be used to relate the structural features of translocated c-myc genes to their tissue-specific transcriptional activation. Protein-DNA interactions on regions of DNA implicated in gene activation will be sought. The consequences for cells of activated c-myc expression also will be studied. Will nonactivated c-myc genes be switched off in such cells because of an autoregulation mechanism? Subtracted cDNA libraries will be constructed using tumor cells that contain translocated c-myc and nontumorigenic cells that are proposed to be their premalignant precursors. This approach may prove more widely applicable to other related cells in tumorigenesis. Finally, I shall employ biological assays that I have developed for c-myc, in order to screen for activated c-myc (and c-myc-like) genes from other tumors, and, in addition, to delineate regions of c-myc protein responsible for its biological effects. (X)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040364-02
Application #
3180218
Study Section
Molecular Biology Study Section (MBY)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Richman, A; Hayday, A (1989) Serum-inducible expression of transfected human c-myc genes. Mol Cell Biol 9:4962-9
Jones, B; Carding, S; Kyes, S et al. (1988) Molecular analysis of T cell receptor gamma gene expression in allo-activated splenic T cells of adult mice. Eur J Immunol 18:1907-15
Jones, B; Mjolsness, S; Janeway Jr, C et al. (1986) Transcripts of functionally rearranged gamma genes in primary T cells of adult immunocompetent mice. Nature 323:635-8