Linked Life Data

20151982

Source:http://linkedlifedata.com/resource/pubmed/id/20151982

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-8-13
pubmed:abstractText
The role of tumor cells in synthesizing pro-inflammatory molecules is still controversial. Here we report that hypoxic treatment of the MCF-7 human mammary adenocarcinoma cell line induced activation of hypoxia-inducible factor 1alpha (HIF-1alpha) and nuclear factor-kappa B (NF-kappaB). Importantly, hypoxia regulated expression of alarmin receptors such as the receptor for advanced glycation end products (RAGE) and the purinoreceptor (P2X7R), and up-regulated inflammatory response (IR) genes such as the inducible enzymes nitric oxide synthase (NOS2), cycloxygenase (COX2), and the acute-phase protein pentraxin-3 (PTX3). Hypoxia also stimulated chemokine (C-X-C motif) receptor 4 (CXCR4) mRNA synthesis. In fact, the CXCR4 ligand stromal-derived factor-1alpha (SDF-1alpha) increased invasion and migration of hypoxic MCF-7 cells. Inhibition of HIF-1alpha by chetomin and NF-kappaB by parthenolide reduced mRNA and protein expression of the studied molecules and prevented invasion of hypoxic MCF-7 cells. Moreover, solid invasive mammary tumor microenvironment was analyzed after laser-capture microdissection (LCMD) comparing tumor versus host normal tissue. Nuclear translocation of HIF-1alpha and NF-kappaB and up-regulation of IR, CXCR4, estrogen receptor alpha (ERalpha), and epithelial growth factor receptor (EGFR) was observed in tumor but not in host normal tissue in the absence of a local inflammatory leukocyte infiltrate. We conclude that under hypoxic conditions MCF-7 cells acquire a pro-inflammatory phenotype, and that solid human mammary carcinoma evidenced a similar activation of HIF-1alpha, NF-kappaB, and IR genes in malignant tumor cells as compared to the normal host tissues. We suggest a role for IR activation in the malignant progression of transformed cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1349-7006
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1014-23
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Up-regulation of pro-inflammatory genes as adaptation to hypoxia in MCF-7 cells and in human mammary invasive carcinoma microenvironment.
pubmed:affiliation
Department of Cellular and Molecular Pathology, IRCCS San Raffaele Pisana, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't