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dc.contributor.authorQuann, K
dc.contributor.authorGonzales, D
dc.contributor.authorMercier, I
dc.contributor.authorWang, C
dc.contributor.authorSotgia, Federica
dc.contributor.authorPestell, R
dc.contributor.authorLisanti, Michael P
dc.contributor.authorJasmin, J
dc.date.accessioned2013-09-25T14:02:30Z
dc.date.available2013-09-25T14:02:30Z
dc.date.issued2013-05-15
dc.identifier.citationCaveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide. 2013, 12 (10):1510-20 Cell Cycleen_GB
dc.identifier.issn1551-4005
dc.identifier.pmid23598719
dc.identifier.doi10.4161/cc.24497
dc.identifier.urihttp://hdl.handle.net/10541/302285
dc.description.abstractCaveolin-1 (Cav-1) is a critical regulator of tumor progression in a variety of cancers where it has been shown to act as either a tumor suppressor or tumor promoter. In glioblastoma multiforme, it has been previously demonstrated to function as a putative tumor suppressor. Our studies here, using the human glioblastoma-derived cell line U-87MG, further support the role of Cav-1 as a negative regulator of tumor growth. Using a lentiviral transduction approach, we were able to stably overexpress Cav-1 in U-87MG cells. Gene expression microarray analyses demonstrated significant enrichment in gene signatures corresponding to downregulation of MAPK, PI3K/AKT and mTOR signaling, as well as activation of apoptotic pathways in Cav-1-overexpressing U-87MG cells. These same gene signatures were later confirmed at the protein level in vitro. To explore the ability of Cav-1 to regulate tumor growth in vivo, we further show that Cav-1-overexpressing U-87MG cells display reduced tumorigenicity in an ectopic xenograft mouse model, with marked hypoactivation of MAPK and PI3K/mTOR pathways. Finally, we demonstrate that Cav-1 overexpression confers sensitivity to the most commonly used chemotherapy for glioblastoma, temozolomide. In conclusion, Cav-1 negatively regulates key cell growth and survival pathways and may be an effective biomarker for predicting response to chemotherapy in glioblastoma.
dc.language.isoenen
dc.rightsArchived with thanks to Cell cycle (Georgetown, Tex.)en_GB
dc.titleCaveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide.en
dc.typeArticleen
dc.contributor.departmentDepartment of Stem Cell Biology & Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.en_GB
dc.identifier.journalCell Cycleen_GB
html.description.abstractCaveolin-1 (Cav-1) is a critical regulator of tumor progression in a variety of cancers where it has been shown to act as either a tumor suppressor or tumor promoter. In glioblastoma multiforme, it has been previously demonstrated to function as a putative tumor suppressor. Our studies here, using the human glioblastoma-derived cell line U-87MG, further support the role of Cav-1 as a negative regulator of tumor growth. Using a lentiviral transduction approach, we were able to stably overexpress Cav-1 in U-87MG cells. Gene expression microarray analyses demonstrated significant enrichment in gene signatures corresponding to downregulation of MAPK, PI3K/AKT and mTOR signaling, as well as activation of apoptotic pathways in Cav-1-overexpressing U-87MG cells. These same gene signatures were later confirmed at the protein level in vitro. To explore the ability of Cav-1 to regulate tumor growth in vivo, we further show that Cav-1-overexpressing U-87MG cells display reduced tumorigenicity in an ectopic xenograft mouse model, with marked hypoactivation of MAPK and PI3K/mTOR pathways. Finally, we demonstrate that Cav-1 overexpression confers sensitivity to the most commonly used chemotherapy for glioblastoma, temozolomide. In conclusion, Cav-1 negatively regulates key cell growth and survival pathways and may be an effective biomarker for predicting response to chemotherapy in glioblastoma.


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