Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-3-8
pubmed:abstractText
Recent evidence suggests that K-ras protooncogene protein p21 may have a tumor-suppressive role in the context of development of lung adenocarcinoma. Levels of K-ras p21, raf-1, mitogen-activated protein kinases Erk 1 and 2, the phosphorylated-activated forms of Erk 1 and 2 (Erk 1P and 2P), and proliferating cell nuclear antigen (PCNA) were measured by immunoblotting in mouse lung tumors (5 to 9 mm in size) caused by N-nitrosodimethylamine (NDMA) and in control lungs. In tumors compared with normal lung, cell membrane-associated K-ras p21 was significantly decreased and cytosolic K-ras p21 increased. Total, membrane, and cytosolic raf-1 and Erk 1P and 2P were increased in tumors compared with normal lung. A single dose of 5 nmol/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given after NDMA resulted in a significant 2.4-fold increase in tumor multiplicity. A significantly greater decrease in membrane-associated K-ras p21 and increase in total and membrane associated raf-1 occurred in the NDMA/TCDD tumors compared with the NDMA-only tumors. PCNA levels increased in tumors, a finding confirmed by immunohistochemistry, and correlated with tumor size after NDMA/TCDD treatment but not after NDMA only. The increase in raf-1 in the tumors was confirmed by immunohistochemistry, which also revealed an increase in raf-1-positive alveolar macrophages specifically associating with tumors from the earliest stages. These results suggest a possible tumor-suppressive function for K-ras p21 in lung and a positive role for raf-1 and Erk 1/2 in lung tumorigenesis. TCDD may promote tumors by contributing to downregulation of K-ras and stimulation of raf-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/Dimethylnitrosamine, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein p21(ras), http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf, http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin, http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein v-RAF1, pig
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
179
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-34
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11884234-Animals, pubmed-meshheading:11884234-Carcinogens, pubmed-meshheading:11884234-DNA Mutational Analysis, pubmed-meshheading:11884234-Dimethylnitrosamine, pubmed-meshheading:11884234-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11884234-Immunoblotting, pubmed-meshheading:11884234-Immunohistochemistry, pubmed-meshheading:11884234-Lung Neoplasms, pubmed-meshheading:11884234-Male, pubmed-meshheading:11884234-Mice, pubmed-meshheading:11884234-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11884234-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:11884234-Mitogen-Activated Protein Kinases, pubmed-meshheading:11884234-Oncogene Protein p21(ras), pubmed-meshheading:11884234-Proliferating Cell Nuclear Antigen, pubmed-meshheading:11884234-Proto-Oncogene Proteins c-raf, pubmed-meshheading:11884234-Tetrachlorodibenzodioxin
pubmed:year
2002
pubmed:articleTitle
Decrease in K-ras p21 and increase in Raf1 and activated Erk 1 and 2 in murine lung tumors initiated by N-nitrosodimethylamine and promoted by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
pubmed:affiliation
Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
pubmed:publicationType
Journal Article