Linked Life Data

16009452

Source:http://linkedlifedata.com/resource/pubmed/id/16009452

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-9-16
pubmed:abstractText
Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an active agent in non-small cell lung cancer, and rapidly relieves bronchorrhea in patients with bronchioloalveolar carcinoma before the improvement of radiological findings. In addition, epidermal growth factor regulates mucin secretion in normal airway goblet cells. The present study was designed to clarify whether gefitinib modifies mucin production in lung cancer cell lines apart from its anti-proliferative effects, using A549 adenocarcinoma and NCI-H292 mucoepidermoid carcinoma cells expressing EGFR and MUC5AC mRNA. Mucin synthesis was measured by RT-PCR and ELISA, and MAPK and Akt, the downstream targets of EGFR, were examined by Western blotting assay. The clinically-achievable concentration of 1muM gefitinib inhibited the growth of both cells by only 10%, but gefitinib suppressed MUC5AC mRNA levels subsequent to a decrease in intracellular and secreted MUC5AC protein. Gefitinib also inhibited the phosphorylation of MAPK and Akt, and the selective inhibitors PD98059 and LY294002 also suppressed MUC5AC protein synthesis. These findings suggest that gefitinib may inhibits MUC5AC synthesis, at least in part, through MAPK and Akt signaling pathways. Thus, gefitinib inhibits mucin production, which is encouraging for trials involving its use against bronchorrhea in patients with lung cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0169-5002
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16009452-Adenocarcinoma, pubmed-meshheading:16009452-Antineoplastic Agents, pubmed-meshheading:16009452-Blotting, Western, pubmed-meshheading:16009452-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:16009452-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:16009452-Humans, pubmed-meshheading:16009452-Lung Neoplasms, pubmed-meshheading:16009452-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:16009452-Mucin 5AC, pubmed-meshheading:16009452-Mucins, pubmed-meshheading:16009452-Oncogene Protein v-akt, pubmed-meshheading:16009452-Phosphorylation, pubmed-meshheading:16009452-Quinazolines, pubmed-meshheading:16009452-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16009452-Signal Transduction, pubmed-meshheading:16009452-Tumor Cells, Cultured
pubmed:year
2005
pubmed:articleTitle
Gefitinib inhibits MUC5AC synthesis in mucin-secreting non-small cell lung cancer cells.
pubmed:affiliation
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. tkita@ma.ejnet.ne.jp
pubmed:publicationType
Journal Article