Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-7-16
pubmed:abstractText
It has become increasingly clear that the cells within the tumor microenvironment play a critical role in cancer growth and metastasis. Studies in experimental models suggest that carcinoma-associated fibroblasts (CAF) differ from normal fibroblasts and are capable of promoting cancer progression through a variety of mechanisms. At present, a definitive view is lacking on whether genomic abnormalities are present and whether they might underlie the observed phenotypic differences. This study reports the molecular analysis of the largest series of breast CAFs reported to date, with an array comparative genomic hybridization-based DNA copy number analysis of cultured CAFs derived from 25 freshly resected human breast cancers. We found DNA copy number changes consisting of the whole arm of chromosomes 6p and 9p plus interstitial 4q loss in only one sample. No abnormalities were observed in non-tumor-associated fibroblast counterparts. Karyotyping of the same CAF revealed further chromosomal abnormalities, which included clonal loss of chromosomes, chromosomal duplications, and less frequent chromosomal rearrangements. These abnormalities were not associated with alterations in the global gene expression profile of this particular CAF, relative to its non-tumor-associated fibroblast counterpart. Moreover, this particular patient's CAF also displayed the only p53 mutation in the cohort, the first time such a mutation has been reported in freshly cultured human CAFs. These findings argue that the procancerous effects of CAFs are unlikely to be due to DNA copy number-type genomic abnormalities in the CAFs themselves. As such, breast CAFs should be mainly regarded as genomically stable cellular constituents that exist within complex cancer microenvironments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
(c)2010 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5770-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Breast carcinoma-associated fibroblasts rarely contain p53 mutations or chromosomal aberrations.
pubmed:affiliation
Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't