Linked Life Data

19010824

Source:http://linkedlifedata.com/resource/pubmed/id/19010824

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-11-17
pubmed:abstractText
The effects of luteinizing hormone (LH), a gonadotropic hormone implicated in the development of ovarian cancer, are mediated by specific binding to its G protein-coupled receptor, the LH receptor (LHR). Activated LHR initiates second messenger responses, including cyclic AMP (cAMP) and inositol phosphate. Because cAMP increases expression of ErbB-2, a receptor tyrosine kinase whose overexpression in cancers correlates with poor survival, we hypothesized that LH may regulate ErbB-2 expression. Cell surface LHR expression in stable transformants of the ErbB-2-overexpressing ovarian cancer cell line SKOV3 was confirmed by PCR and whole-cell ligand binding studies. Second messenger accumulation in the LHR-expressing cells confirmed signaling through Gs and Gq. Western blots of total protein revealed that LHR introduction up-regulated ErbB-2 protein expression 2-fold and this was further up-regulated in a time- and dose-dependent manner in response to LH. Forskolin and 8Br-cAMP also up-regulated ErbB-2 in both LHR-expressing and mock-transfected cells, indicating that regulation of ErbB-2 is a cAMP-mediated event. Kinase inhibitor studies indicated the involvement of protein kinase A-mediated, protein kinase C-mediated, epidermal growth factor receptor-mediated, and ErbB-2-mediated mechanisms. The LH-induced up-regulation of ErbB-2 was insufficient to overcome the negative effects of LH on proliferation, invasion, and migration. A molecular signature for this nonaggressive phenotype was determined by Taqman array to include increased and decreased expression of genes encoding adhesion proteins and metalloproteinases, respectively. These data establish a role for LH and LHR in the regulation of ErbB-2 expression and suggest that, in some systems, ErbB-2 up-regulation alone is insufficient in producing a more aggressive phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1775-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19010824-8-Bromo Cyclic Adenosine Monophosphate, pubmed-meshheading:19010824-Cell Line, Tumor, pubmed-meshheading:19010824-Cell Movement, pubmed-meshheading:19010824-Cell Proliferation, pubmed-meshheading:19010824-Cyclic AMP, pubmed-meshheading:19010824-Female, pubmed-meshheading:19010824-Forskolin, pubmed-meshheading:19010824-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19010824-Genes, erbB-2, pubmed-meshheading:19010824-Humans, pubmed-meshheading:19010824-Inositol Phosphates, pubmed-meshheading:19010824-Luteinizing Hormone, pubmed-meshheading:19010824-Neoplasm Invasiveness, pubmed-meshheading:19010824-Ovarian Neoplasms, pubmed-meshheading:19010824-Protein Kinase Inhibitors, pubmed-meshheading:19010824-Receptor, erbB-2, pubmed-meshheading:19010824-Receptors, LH, pubmed-meshheading:19010824-Signal Transduction, pubmed-meshheading:19010824-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Luteinizing hormone-induced up-regulation of ErbB-2 is insufficient stimulant of growth and invasion in ovarian cancer cells.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural