Linked Life Data

14516786

Source:http://linkedlifedata.com/resource/pubmed/id/14516786

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-9-30
pubmed:abstractText
Aging is the highest risk factor for cancer. Although oxidants are thought to contribute to both aging and cancer, the interplay between oxidative stress, aging, and cancer has not been well studied. Human diploid fibroblasts (HDFs) undergo premature senescence in response to sublethal doses of H(2)O(2). To test the hypothesis that senescent or senescent-like HDFs function as a tumor promoter, we have employed an in vitro skin tumor promotion model, in which colony formation is measured using initiated mouse keratinocyte 308 cells seeded at clonal density. 308 cells form colonies when co-cultured with normal HDFs only in the presence of the tumor promoter phorbol 12-myristate 13-acetate (TPA), which induces an average of 5.75 colonies. When co-cultured with H(2)O(2)-treated HDFs, 308 cells form an average of 30.3 colonies. To understand the mechanism behind this phenomenon, we tested whether conditioned medium of HDFs, HDF extracellular matrix (ECM), density of HDFs, or the contact between keratinocytes and HDFs plays a role in 308 cell colony formation. The conditioned medium from prematurely senescent cells resulted in an average of eightfold more 308 cell colonies formed than the conditioned medium from normal HDFs, and the growth-promoting effect of the conditioned medium was trypsin sensitive. The ECM alone was not able to induce 308 cell colony formation. Increasing the density of normal HDFs or contact with normal HDFs but not senescent-like HDFs was inhibitory to the growth of 308 cells. Measurement of Connexin 43 indicated a decreased expression of the protein, which suggests an impaired gap junction communication in senescent-like HDFs. We conclude that H(2)O(2)-treated fibroblasts not only lose contact inhibition of the growth of initiated keratinocytes perhaps related to reduced gap junction communication but also increase production of secreted protein factors to enhance the growth of 308 keratinocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-48
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14516786-Carcinogens, pubmed-meshheading:14516786-Cell Adhesion, pubmed-meshheading:14516786-Cell Aging, pubmed-meshheading:14516786-Cell Communication, pubmed-meshheading:14516786-Cell Division, pubmed-meshheading:14516786-Cell Line, pubmed-meshheading:14516786-Cell Transformation, Neoplastic, pubmed-meshheading:14516786-Coculture Techniques, pubmed-meshheading:14516786-Connexin 43, pubmed-meshheading:14516786-Culture Media, Conditioned, pubmed-meshheading:14516786-Extracellular Matrix, pubmed-meshheading:14516786-Fibroblasts, pubmed-meshheading:14516786-Gap Junctions, pubmed-meshheading:14516786-Humans, pubmed-meshheading:14516786-Keratinocytes, pubmed-meshheading:14516786-Models, Biological, pubmed-meshheading:14516786-Neoplasms, pubmed-meshheading:14516786-Oxidants, pubmed-meshheading:14516786-Oxidative Stress, pubmed-meshheading:14516786-Tetradecanoylphorbol Acetate, pubmed-meshheading:14516786-Tumor Stem Cell Assay
pubmed:year
2003
pubmed:articleTitle
Novel mechanisms of sublethal oxidant toxicity: induction of premature senescence in human fibroblasts confers tumor promoter activity.
pubmed:affiliation
Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't