Linked Life Data

11289112

Source:http://linkedlifedata.com/resource/pubmed/id/11289112

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-4-5
pubmed:abstractText
Normal epithelial cells are anchorage-dependent. Detachment of normal epithelial cells from their substratum causes apoptosis, termed anoikis. Malignant tumor cells, however, can survive and proliferate independent of anchorage. To understand the molecular basis of tumor cell anchorage independence, we investigated the role of tyrosine kinases and their downstream signaling pathways in anoikis resistance of human lung adenocarcinoma cells. Four of the five lung adenocarcinoma cell lines analyzed are resistant to anoikis. Tyrosine kinase inhibitor genistein rendered three of them sensitive to anoikis. Although cell detachment induced rapid protein tyrosine dephosphorylation in Madin-Darby canine kidney cells, a nontransformed epithelial cell line, tyrosine phosphorylation of several proteins in the tumor cells is anchorage-independent. Similarly, phosphorylation of Akt and mitogen-activated protein kinase, two signaling proteins downstream of tyrosine kinases, was decreased in Madin-Darby canine kidney cells but increased in some of the tumor cells upon cell detachment. Inhibition of phosphorylation of the two proteins, however, did not induce anoikis in the tumor cells. Specific inhibitors to several known tyrosine kinases also failed to induce anoikis in these cells. These data suggest the existence of tyrosine kinase-dependent phosphatidylinositol 3'-kinase and mitogen-activated protein kinase-independent signaling pathways that function to regulate cell survival and death. Alteration in these pathways may count for the anchorage-independent survival of the lung adenocarcinoma cells and other malignant tumor cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2439-44
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11289112-Adenocarcinoma, pubmed-meshheading:11289112-Anoikis, pubmed-meshheading:11289112-Cell Adhesion, pubmed-meshheading:11289112-Cell Survival, pubmed-meshheading:11289112-Enzyme Inhibitors, pubmed-meshheading:11289112-Genistein, pubmed-meshheading:11289112-Humans, pubmed-meshheading:11289112-Lung Neoplasms, pubmed-meshheading:11289112-MAP Kinase Signaling System, pubmed-meshheading:11289112-Mitogen-Activated Protein Kinases, pubmed-meshheading:11289112-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11289112-Phosphorylation, pubmed-meshheading:11289112-Protein-Serine-Threonine Kinases, pubmed-meshheading:11289112-Proto-Oncogene Proteins, pubmed-meshheading:11289112-Proto-Oncogene Proteins c-akt, pubmed-meshheading:11289112-Substrate Specificity, pubmed-meshheading:11289112-Tumor Cells, Cultured, pubmed-meshheading:11289112-Tyrosine
pubmed:year
2001
pubmed:articleTitle
Tyrosine kinase-dependent, phosphatidylinositol 3'-kinase, and mitogen-activated protein kinase-independent signaling pathways prevent lung adenocarcinoma cells from anoikis.
pubmed:affiliation
Pulmonary Center, Department of Medicine, Boston University Medical Center, Massachusetts 02118, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.