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Article: Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model

TitleFlotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model
Authors
KeywordsMMTV-PyMT
reggie1/2
Breast cancer
flotillin-1
metastasis
Issue Date2013
Citation
Oncogene, 2013, v. 32, n. 41, p. 4989-4994 How to Cite?
AbstractFlotillin microdomains, specialized lipid raft domains in cell membranes, serve as physical platforms for many different molecules important in crucial intracellular signaling pathways. Flotillin-2 (Flot2), together with flotillin-1, is a marker for lipid raft microdomains distinct from caveolar lipid rafts, and has been implicated in the progression of cancer and metastasis formation. Based largely on studies in xenograft models, flotillin-2 has been implicated in the progression of multiple types of human tumors, including breast cancer. In our studies, we identified flotillin-2 as highly amplified in a high-throughput comparative genomic hybridization screen of human breast cancer cell lines and breast tumor samples. Short hairpin RNA-mediated reduction of flotillin-2 protein levels significantly reduced the tumorigenicity and metastatic capability of a human breast cancer cell line in vivo. We generated mice deficient for flotillin-2 and also found a reduction of flotillin-1 protein levels and complete absence of flotillin-specific membrane microdomains in these mice. To examine the role of Flot2 in mammary tumorigenesis and lung metastasis, we used an in vivo molecular genetics approach, crossing a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with gene-targeted Flot2 -/- mice. Flotillin-2 deficiency lead to a striking reduction in the number of lung metastasis observed, but had no influence on primary tumor formation in this model. Our results indicate, using a novel in vivo animal model approach, that Flot2 is an important regulator of mammary tumor-derived lung metastasis. © 2013 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/292777
ISSN
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 2.334
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBerger, T.-
dc.contributor.authorUeda, T.-
dc.contributor.authorArpaia, E.-
dc.contributor.authorChio, I. I.C.-
dc.contributor.authorShirdel, E. A.-
dc.contributor.authorJurisica, I.-
dc.contributor.authorHamada, K.-
dc.contributor.authorYou-Ten, A.-
dc.contributor.authorHaight, J.-
dc.contributor.authorWakeham, A.-
dc.contributor.authorCheung, C. C.-
dc.contributor.authorMak, T. W.-
dc.date.accessioned2020-11-17T14:57:12Z-
dc.date.available2020-11-17T14:57:12Z-
dc.date.issued2013-
dc.identifier.citationOncogene, 2013, v. 32, n. 41, p. 4989-4994-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/292777-
dc.description.abstractFlotillin microdomains, specialized lipid raft domains in cell membranes, serve as physical platforms for many different molecules important in crucial intracellular signaling pathways. Flotillin-2 (Flot2), together with flotillin-1, is a marker for lipid raft microdomains distinct from caveolar lipid rafts, and has been implicated in the progression of cancer and metastasis formation. Based largely on studies in xenograft models, flotillin-2 has been implicated in the progression of multiple types of human tumors, including breast cancer. In our studies, we identified flotillin-2 as highly amplified in a high-throughput comparative genomic hybridization screen of human breast cancer cell lines and breast tumor samples. Short hairpin RNA-mediated reduction of flotillin-2 protein levels significantly reduced the tumorigenicity and metastatic capability of a human breast cancer cell line in vivo. We generated mice deficient for flotillin-2 and also found a reduction of flotillin-1 protein levels and complete absence of flotillin-specific membrane microdomains in these mice. To examine the role of Flot2 in mammary tumorigenesis and lung metastasis, we used an in vivo molecular genetics approach, crossing a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with gene-targeted Flot2 -/- mice. Flotillin-2 deficiency lead to a striking reduction in the number of lung metastasis observed, but had no influence on primary tumor formation in this model. Our results indicate, using a novel in vivo animal model approach, that Flot2 is an important regulator of mammary tumor-derived lung metastasis. © 2013 Macmillan Publishers Limited All rights reserved.-
dc.languageeng-
dc.relation.ispartofOncogene-
dc.subjectMMTV-PyMT-
dc.subjectreggie1/2-
dc.subjectBreast cancer-
dc.subjectflotillin-1-
dc.subjectmetastasis-
dc.titleFlotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/onc.2012.499-
dc.identifier.pmid23146906-
dc.identifier.scopuseid_2-s2.0-84885572182-
dc.identifier.volume32-
dc.identifier.issue41-
dc.identifier.spage4989-
dc.identifier.epage4994-
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000325717800015-
dc.identifier.issnl0950-9232-

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