Evidence map›Paper›PMID 16767161›Full record

ArticleOncogene2006

Methylation of the p16(INK4a) promoter region in telomerase immortalized human keratinocytes co-cultured with feeder cells.

B W Darbro, K M Lee, N K Nguyen, F E Domann, A J Klingelhutz

Abstract read
In one paragraph

Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. ARHGAP29 promotes keratinocyte proliferation and migration in vitro and is dispensable for in vivo wound healing.Developmental dynamics : an official publication of the American Association of Anatomists · 2025
    Article
  2. Article
  3. Article
  4. Low p16The Prostate · 2017
    Article
  5. Immortalization of human normal and NF1 neurofibroma Schwann cells.Laboratory investigation; a journal of technical methods and pathology · 2016
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

B W DarbroInterdisciplinary Program in Molecular Biology and Medical Scientist Training Program, University of Iowa, Iowa City, IA 52242, USA.
K M Lee
N K Nguyen
F E Domann
A J Klingelhutz

Funding

Multidisciplinary Lung Research Career Development ProgramT32HL007638 · NHLBI · UNIVERSITY OF IOWA · PI WELSH, MICHAEL J., ZABNER, JOSEPH · 1986 to 2020
$16.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007337 · NIGMS · UNIVERSITY OF IOWA · PI GEYER, PAMELA K., LENTZ, STEVEN R · 1985 to 2020
$15.9M
Epigenetic factors governing SOD2 gene expressionR01CA073612 · NCI · UNIVERSITY OF IOWA · PI DOMANN, FREDERICK E · 2003 to 2007
$1.3M
OVERCOMING CELLULAR SENESCENCE IN HUMAN EPITHELIAL CELLSR01AG018265 · NIA · UNIVERSITY OF IOWA · PI KLINGELHUTZ, ALOYSIUS JOHN · 2000 to 2004
$1.2M
NCI NIH HHS R01 CA073612NCI NIH HHS R01 CA73612NHLBI NIH HHS T32 HL007638NHLBI NIH HHS T32 HL07638NIA NIH HHS R01 AG018265NIA NIH HHS R01 AG18265NIGMS NIH HHS T32 GM007337NIGMS NIH HHS T32 GM07337
6 · The paper itself

Abstract

Human keratinocytes grown in co-culture with fibroblast feeder cells have an extended in vitro lifespan and delayed accumulation of the tumor suppressor protein p16(INK4a) when compared to the same cells grown on tissue culture plastic alone. Previous studies have indicated that human keratinocytes can be immortalized by telomerase activity alone when grown in co-culture with feeder cells, suggesting that loss of the p16(INK4a)/Rb pathway is not required for immortalization. Using two independent human keratinocyte cell strains, we found that exogenous telomerase expression and co-culture with feeder cells results in efficient extension of lifespan without an apparent crisis. However, when these cells were transferred from the co-culture environment to plastic alone they experienced only a brief period of slowed growth before continuing to proliferate indefinitely. Examination of immortal cell lines demonstrated p16(INK4a) promoter methylation had occurred in both the absence and presence of feeder cells. Reintroduction of p16(INK4a) into immortal cell lines resulted in rapid growth arrest. Our results suggest that p16(INK4a)/Rb-induced telomere-independent senescence, although delayed in the presence of feeders, still provides a proliferation barrier to human keratinocytes in this culture system and that extended culture of telomerase-transduced keratinocytes on feeders can lead to the methylation of p16(INK4a).

Indexed as

DNA MethylationPromoter Regions, GeneticBase SequenceCell Line, TransformedCoculture TechniquesCyclin-Dependent Kinase Inhibitor p16DNA PrimersHumansImmunohistochemistryKeratinocytesReverse Transcriptase Polymerase Chain ReactionTelomeraseCyclin-Dependent Kinase Inhibitor p16DNA PrimersTelomerase

Identifiers

PMID16767161
PMCPMC1894570

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.