PMID- 12807723
OWN - NLM
STAT- MEDLINE
DCOM- 20030822
LR  - 20210319
IS  - 0143-3334 (Print)
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 24
IP  - 7
DP  - 2003 Jul
TI  - Extended lifespan of Barrett's esophagus epithelium transduced with the human 
      telomerase catalytic subunit: a useful in vitro model.
PG  - 1183-90
AB  - As there has been no previous information on the consequences of telomerase 
      expression in genetically altered, mortal cells derived from pre-malignant 
      tissue, we sought to determine the effect of hTERT (human catalytic subunit of 
      telomerase reverse transcriptase) transduction of pre-malignant cell strains from 
      Barrett's esophagus that do not contain telomerase activity and possess a finite 
      lifespan. Primary cultures of Barrett's esophageal epithelium transduced with a 
      retrovirus containing hTERT were characterized by growth factor requirements, 
      cytogenetics and flow cytometry. Expression of telomerase lengthened telomeres 
      and greatly extended the lifespan of hTERT transduced (hTERT+) Barrett's 
      esophagus cells. Growth factor dependency of the hTERT+ cultures remained largely 
      similar to the parental cultures, although there was a modest increase in the 
      ability to grow in agar. Chromosomal instability, measured by both karyotypic and 
      FISH (fluorescence in situ hybridization) analyses, was reduced but not abrogated 
      by hTERT transduction, suggesting that telomerase expression can enhance genomic 
      stability. However, the persistence of residual instability gave rise to new 
      clonal and non-clonal genetic variants, and in one hTERT+ culture a new DNA 
      aneuploid population was observed, the only time such a ploidy shift has been 
      seen in Barrett's cell strains in vitro. These in vitro observations are 
      analogous to the clinical progression to aneuploidy that often precedes cancer in 
      Barrett's esophagus, and suggest that reactivation of telomerase may be 
      permissive for continued genetic evolution to cancer. Long-lived Barrett's 
      esophagus epithelial cultures should provide a useful in vitro model for studies 
      of neoplastic evolution and chemopreventive therapies.
FAU - Palanca-Wessels, M Corinna A
AU  - Palanca-Wessels MC
AD  - Department of Pathology, University of Washington, Seattle, Washington, USA.
FAU - Klingelhutz, Aloysius
AU  - Klingelhutz A
FAU - Reid, Brian J
AU  - Reid BJ
FAU - Norwood, Thomas H
AU  - Norwood TH
FAU - Opheim, Kent E
AU  - Opheim KE
FAU - Paulson, Thomas G
AU  - Paulson TG
FAU - Feng, Ziding
AU  - Feng Z
FAU - Rabinovitch, Peter S
AU  - Rabinovitch PS
LA  - eng
GR  - R01 CA061202/CA/NCI NIH HHS/United States
GR  - R01 CA78855/CA/NCI NIH HHS/United States
GR  - T32 AG00057/AG/NIA NIH HHS/United States
GR  - R01 CA61202/CA/NCI NIH HHS/United States
GR  - T32 AG000057/AG/NIA NIH HHS/United States
GR  - P01 CA91955/CA/NCI NIH HHS/United States
GR  - P01 CA091955/CA/NCI NIH HHS/United States
GR  - P01 AG001751/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030509
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (DNA-Binding Proteins)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Barrett Esophagus/*genetics/*pathology
MH  - Cell Adhesion
MH  - Cell Division
MH  - Cell Transformation, Neoplastic/*pathology
MH  - Chromosome Aberrations
MH  - Colony-Forming Units Assay
MH  - DNA-Binding Proteins
MH  - Epithelial Cells/pathology
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - In Vitro Techniques
MH  - Karyotyping
MH  - Retroviridae/genetics
MH  - Telomerase/*genetics
MH  - Telomere/metabolism
MH  - Transduction, Genetic
MH  - Transfection
PMC - PMC1559990
MID - NIHMS11541
EDAT- 2003/06/17 05:00
MHDA- 2003/08/23 05:00
PMCR- 2008/01/28
CRDT- 2003/06/17 05:00
PHST- 2003/06/17 05:00 [pubmed]
PHST- 2003/08/23 05:00 [medline]
PHST- 2003/06/17 05:00 [entrez]
PHST- 2008/01/28 00:00 [pmc-release]
AID - bgg076 [pii]
AID - 10.1093/carcin/bgg076 [doi]
PST - ppublish
SO  - Carcinogenesis. 2003 Jul;24(7):1183-90. doi: 10.1093/carcin/bgg076. Epub 2003 May 
      9.