Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-9-17
pubmed:abstractText
Cyclin D1 dysregulation and differential inactivation of p16INK4a and Rb have been observed in human lung cancer. In chemically induced mouse lung tumors, the p16INK4a gene is a target of inactivation, and Rb is reduced at the mRNA level (Northern blot) although similar at the protein level (Western blot) when compared to normal lung tissues. The expression of cyclin D1, cdk4, p16INK4a, and Rb protein was examined by immunohistochemistry in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse lung tumors. Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D1 and cdk4 that was light to moderate in normal mouse lung tissues, but intense in lung adenomas and adenocarcinomas. Western blot analysis confirmed the increased expression of cyclin D1 and cdk4 in lung tumors compared to normal lung. Immunohistochemical analyses of lung tumors showed focal areas which lacked p16INK4a staining. Expression of p16INK4a, as determined by RT-PCR, was variable in lung tumors. Mutations in p16INK4a were not found by SSCP analysis. Immunohistochemical analyses of normal lung tissues showed intense staining for Rb protein in alveolar epithelial cells and in other lung cell types; however, in the lung tumors the staining intensity was reduced and the distribution was altered. Expression of Rb was detected in normal lung tissues but was barely detectable by Northern blot hybridization in lung tumors. Western blot analysis indicated the presence of both hypophosphorylated and hyperphosphorylated Rb protein in lung tumors and in normal lung tissues. These results suggest that alterations in the cell cycle proteins, cyclin D1, cdk4, p16INK4a, and Rb, may play a role in the acquisition of autonomous growth by adenomas. Furthermore, they demonstrate the importance of immunohistochemical studies to examine expression in tissues that contain multiple cell types, such as the lung, and in tumors that by nature are heterogeneous.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0190-2148
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
499-521
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9659580-Adenocarcinoma, pubmed-meshheading:9659580-Adenoma, pubmed-meshheading:9659580-Animals, pubmed-meshheading:9659580-Blotting, Western, pubmed-meshheading:9659580-Cell Cycle Proteins, pubmed-meshheading:9659580-Cyclin D1, pubmed-meshheading:9659580-Cyclin-Dependent Kinase Inhibitor p16, pubmed-meshheading:9659580-Cyclin-Dependent Kinases, pubmed-meshheading:9659580-DNA Mutational Analysis, pubmed-meshheading:9659580-DNA Primers, pubmed-meshheading:9659580-Immunoenzyme Techniques, pubmed-meshheading:9659580-Lung, pubmed-meshheading:9659580-Lung Neoplasms, pubmed-meshheading:9659580-Male, pubmed-meshheading:9659580-Mice, pubmed-meshheading:9659580-Mice, Inbred A, pubmed-meshheading:9659580-Nitrosamines, pubmed-meshheading:9659580-Polymerase Chain Reaction, pubmed-meshheading:9659580-RNA, Messenger, pubmed-meshheading:9659580-Retinoblastoma Protein
pubmed:articleTitle
Expression of cell cycle proteins in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung tumors.
pubmed:affiliation
Division of Environmental Health Sciences, School of Public Health, Ohio State University, Columbus, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.