Source:http://linkedlifedata.com/resource/pubmed/id/16799078
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2006-9-8
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pubmed:abstractText |
RATIONALE: Analogous to the adenoma-carcinoma sequence in the colon, it has been proposed that adenocarcinoma (AC) in the lung arises from adenomatous hyperplasia that progresses through atypical adenomatous hyperplasia to AC. However, the data supporting this sequence are largely circumstantial and the almost impossible task of identifying these lesions before resection rules out any longitudinal study in humans. OBJECTIVES, METHODS, AND RESULTS: We show in mice that the loss of function of the neurokinin-1 receptor (NK-1R)-due to either a pharmacologic or genetic manipulation-results in a sequence of morphologic changes in response to bleomycin treatment that precede the development of AC. We also demonstrate that a series of alterations in gene expression of proliferation markers (i.e., PCNA and Ki-67) and cell cycle regulators (i.e., FHIT, p53, and p21) characterizes the sequence of the precursor lesions. The loss of function of the NK-1R results in changes of the apoptotic rate and in a delay of DNA break recovery of alveolar epithelial cells following bleomycin treatment. The NK-1R blockade interferes with a caspase-independent pathway of apoptosis by affecting both the translocation of Nur77 into the cytoplasm and the expression of some important Bcl2 family members such as Bcl2 and Bak. CONCLUSIONS: To our knowledge, this is the first model to demonstrate a role for NK-1R in lung epithelial cell death and tumorigenesis. This animal model may provide new information on the biology of AC and will facilitate designing and testing of new therapeutic interventions.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Ki-67 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1073-449X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
174
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
674-83
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16799078-Adenocarcinoma,
pubmed-meshheading:16799078-Animals,
pubmed-meshheading:16799078-Antibiotics, Antineoplastic,
pubmed-meshheading:16799078-Apoptosis,
pubmed-meshheading:16799078-Bleomycin,
pubmed-meshheading:16799078-DNA, Neoplasm,
pubmed-meshheading:16799078-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16799078-Genes, p53,
pubmed-meshheading:16799078-Immunohistochemistry,
pubmed-meshheading:16799078-Ki-67 Antigen,
pubmed-meshheading:16799078-Lung Neoplasms,
pubmed-meshheading:16799078-Mice,
pubmed-meshheading:16799078-Mice, Inbred BALB C,
pubmed-meshheading:16799078-Mice, Inbred C57BL,
pubmed-meshheading:16799078-Mice, Knockout,
pubmed-meshheading:16799078-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:16799078-Protein-Tyrosine Kinases,
pubmed-meshheading:16799078-Proto-Oncogene Proteins,
pubmed-meshheading:16799078-Receptors, Neurokinin-1
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pubmed:year |
2006
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pubmed:articleTitle |
Neurokinin-1 receptor blockade and murine lung tumorigenesis.
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pubmed:affiliation |
Department of Physiopathology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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