PMID- 9780006
OWN - NLM
STAT- MEDLINE
DCOM- 19981123
LR  - 20071114
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 17
IP  - 7
DP  - 1998 Aug 20
TI  - Reduced telomeric signals and increased telomeric associations in human lung 
      cancer cell lines undergoing p53-mediated apoptosis.
PG  - 901-6
AB  - Transduction of a p53-negative H1299 human non-small cell lung cancer cell line 
      with an adenoviral vector containing wild-type p53 (Ad5p53) induced apoptosis. 
      Analysis of the Ad5p53-infected H1299 cells showed high levels of telomeric 
      association prior to apoptotic nuclear fragmentation. Similar telomeric 
      association was observed in stably transfected clones of the wtH226b cell line, 
      which expressed exogenous wild-type p53 protein and also showed complex 
      chromosomal abnormalities including dicentrics, rings and fragments. Fluorescence 
      in situ hybridization (FISH) analysis using a human telomeric DNA probe indicated 
      reductions in telomere signals in both Ad5p53-infected H1299 cells and wtH226b-S 
      cells. In contrast, stably transfected wtH226b-AS clones expressing antisense p53 
      cDNA showed no telomeric association and had high levels of telomeric signals 
      associated with a faster growing phenotype. These results suggest that wild-type 
      p53 is involved in shortening telomeres, a possibly early event in the 
      p53-mediated apoptotic process and in the subsequent telomeric association that 
      predisposes a cell to genetic instability and DNA fragmentation resulting in 
      apoptotic cell death. Moreover, loss of telomeric signals may indicate a cell's 
      decision to undergo programmed cell death and, if so, could, serve as a sensitive 
      marker of p53-mediated apoptosis.
FAU - Mukhopadhyay, T
AU  - Mukhopadhyay T
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD 
      Anderson Cancer Center, Houston 77030, USA.
FAU - Multani, A S
AU  - Multani AS
FAU - Roth, J A
AU  - Roth JA
FAU - Pathak, S
AU  - Pathak S
LA  - eng
GR  - CA 16672/CA/NCI NIH HHS/United States
GR  - P50-CA70907/CA/NCI NIH HHS/United States
GR  - R01 CA45187/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adenoviruses, Human/genetics
MH  - Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology
MH  - Chromosome Aberrations
MH  - Chromosome Banding
MH  - Chromosome Disorders
MH  - *Genes, p53
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Kinetics
MH  - Lung Neoplasms/*genetics/pathology
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction
MH  - Telomere/genetics/*physiology
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*metabolism
EDAT- 1998/10/21 00:00
MHDA- 1998/10/21 00:01
CRDT- 1998/10/21 00:00
PHST- 1998/10/21 00:00 [pubmed]
PHST- 1998/10/21 00:01 [medline]
PHST- 1998/10/21 00:00 [entrez]
AID - 10.1038/sj.onc.1202011 [doi]
PST - ppublish
SO  - Oncogene. 1998 Aug 20;17(7):901-6. doi: 10.1038/sj.onc.1202011.