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Cell Cycle. 2013 May 15;12(10):1510-20. doi: 10.4161/cc.24497. Epub 2013 Apr 17.

Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide.

Author information

1
Department of Stem Cell Biology & Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Abstract

Caveolin-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.

KEYWORDS:

Caveolin-1; brain cancer; chemotherapy; glioma; microarray; mouse model; temozolomide; tumor progression; tumor suppressor

PMID:
23598719
PMCID:
PMC3680531
DOI:
10.4161/cc.24497
[Indexed for MEDLINE]
Free PMC Article

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