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Article: Disruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis

TitleDisruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis
Authors
KeywordsMouse mammary tumor virus-polyoma middle T antigen
Breast cancer
Lipocalin-2
Matrix metalloproteinase-9
Issue Date2010
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2010, v. 107, n. 7, p. 2995-3000 How to Cite?
AbstractBased largely on studies in xenograft models, lipocalin-2 (Lcn2) has been implicated in the progression of multiple types of human tumors, including breast cancer. Here we examine the role of Lcn2 in mammary tumorigenesis and lung metastasis using an in vivo molecular genetics approach. We crossed a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with two independent gene-targeted Lcn2-/- mouse strains of the 129/Ola or C57BL/6 genetic background. The onset and progression of mammary tumor development and lung metastasis in the female progeny of these crosses were monitored over a 20-week period. Female Lcn2-/-MMTV-PyMT mice of the 129/Ola background (Lcn2-/-PyMT129) showed delayed onset of mammary tumors, and both Lcn2-/-PyMT129 mice and Lcn2-/-MMTV-PyMT mice of the C57BL/6 background (Lcn2-/-PyMTB6) exhibited signi.cant decreases in multiplicity and tumor burden (∼2- to 3-fold), as measured by total tumor weight and volume. At the molecular level, mammary tumors derived from Lcn2-/-PyMTB6 females showed reduced matrix metalloproteinase-9 (MMP-9) activity and a lack of high molecular weight MMP activity. However, although increased MMP-9 activity has been linked to tumor progression, neither Lcn2-/-PyMTB6 nor Lcn2 -/-PyMT129 female mice showed a reduction in lung metastases compared to Lcn2+/+PyMT controls. Our results demonstrate, using an in vivo animal model approach, that Lcn2 is a potent inducer of mammary tumor growth but not a significant promoter of lung metastasis.
Persistent Identifierhttp://hdl.handle.net/10722/291947
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBerger, Thorsten-
dc.contributor.authorCheung, Carol C.-
dc.contributor.authorElia, Andrew J.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:55:26Z-
dc.date.available2020-11-17T14:55:26Z-
dc.date.issued2010-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2010, v. 107, n. 7, p. 2995-3000-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/291947-
dc.description.abstractBased largely on studies in xenograft models, lipocalin-2 (Lcn2) has been implicated in the progression of multiple types of human tumors, including breast cancer. Here we examine the role of Lcn2 in mammary tumorigenesis and lung metastasis using an in vivo molecular genetics approach. We crossed a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with two independent gene-targeted Lcn2-/- mouse strains of the 129/Ola or C57BL/6 genetic background. The onset and progression of mammary tumor development and lung metastasis in the female progeny of these crosses were monitored over a 20-week period. Female Lcn2-/-MMTV-PyMT mice of the 129/Ola background (Lcn2-/-PyMT129) showed delayed onset of mammary tumors, and both Lcn2-/-PyMT129 mice and Lcn2-/-MMTV-PyMT mice of the C57BL/6 background (Lcn2-/-PyMTB6) exhibited signi.cant decreases in multiplicity and tumor burden (∼2- to 3-fold), as measured by total tumor weight and volume. At the molecular level, mammary tumors derived from Lcn2-/-PyMTB6 females showed reduced matrix metalloproteinase-9 (MMP-9) activity and a lack of high molecular weight MMP activity. However, although increased MMP-9 activity has been linked to tumor progression, neither Lcn2-/-PyMTB6 nor Lcn2 -/-PyMT129 female mice showed a reduction in lung metastases compared to Lcn2+/+PyMT controls. Our results demonstrate, using an in vivo animal model approach, that Lcn2 is a potent inducer of mammary tumor growth but not a significant promoter of lung metastasis.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectMouse mammary tumor virus-polyoma middle T antigen-
dc.subjectBreast cancer-
dc.subjectLipocalin-2-
dc.subjectMatrix metalloproteinase-9-
dc.titleDisruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1000101107-
dc.identifier.pmid20133630-
dc.identifier.pmcidPMC2840296-
dc.identifier.scopuseid_2-s2.0-77649268223-
dc.identifier.volume107-
dc.identifier.issue7-
dc.identifier.spage2995-
dc.identifier.epage3000-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000274599500053-
dc.identifier.issnl0027-8424-

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