Abstract

The factors that cause cancer to be a major health problem of the elderly are unknown. We are addressing this problem by studying aging at the molecular level using cellular models. We have shown that defects in the senescence program in tumor cells is corrected by introduction of specific normal human chromosomes, including chromosomes 1,2, and 3. We are cloning these putative senescence genes by combining several approaches including radiation reduction hybrids, TAR cloning, subtractive hybridization, and cDNA microarray analysis. This is the final year for this project - continuing research will be performed at NCI.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES023003-10
Application #
6432266
Study Section
(LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Zhang, J; Zhang, L X; Meltzer, P S et al. (2000) Molecular cloning of human Hic-5, a potential regulator involved in signal transduction and cellular senescence. Mol Carcinog 27:177-83
Humble, M C; Kouprina, N; Noskov, V N et al. (2000) Radial transformation-associated recombination cloning from the mouse genome: isolation of Tg.AC transgene with flanking DNAs. Genomics 70:292-9
Devereux, T R; Horikawa, I; Anna, C H et al. (1999) DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res 59:6087-90
Horikawa, I; Cable, P L; Afshari, C et al. (1999) Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res 59:826-30
Tanaka, H; Horikawa, I; Kugoh, H et al. (1999) Telomerase-independent senescence of human immortal cells induced by microcell-mediated chromosome transfer. Mol Carcinog 25:249-55
Bertram, M J; Berube, N G; Hang-Swanson, X et al. (1999) Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes. Mol Cell Biol 19:1479-85
Isaacs, J S; Barrett, J C; Weissman, B E (1999) Interference of proteins involved in the cytoplasmic sequestration of p53 with human papillomavirus E6-mediated degradation. Mol Carcinog 24:70-7
Larionov, V (1999) Direct isolation of specific chromosomal regions and entire genes by TAR cloning. Genet Eng (N Y) 21:37-55
Burkhart, B A; Alcorta, D A; Chiao, C et al. (1999) Two posttranscriptional pathways that regulate p21(Cip1/Waf1/Sdi1) are identified by HPV16-E6 interaction and correlate with life span and cellular senescence. Exp Cell Res 247:168-75