Human Caveolin-1 and Caveolin-2 Are Closely Linked Genes Colocalized with WI-5336 in a Region of 7q31 Frequently Deleted in Tumors

Fra, Annamaria; Mastroianni, Nadia; Mancini, Mita; Pasqualetto, Elena; Sitia, Roberto

doi:10.1006/geno.1998.5723

Cited by 23 publications

(16 citation statements)

References 6 publications

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“…Collectively, these data imply that caveolin-1 may function in a tumor suppressor capacity. This interpretation is consistent with data that map the caveolin-1 gene to a fragile region, 7q31.1, often deleted in tumors (Lin et al, 1996;Engelman et al, 1998;Fra et al, 1999Fra et al, , 2000Hurlstone et al, 1999). However, many types of human cancers (Hatanaka et al, 1998;Lavie et al, 1998;Yang CPH et al, 1998), including human prostate cancer as well as primary and metastatic breast cancer, show an elevation, rather than a reduction, in the expression levels of caveolin-1 mRNA and protein.…”

Section: Introductionsupporting

confidence: 84%

“…Some of the most frequent chromosomal abnormalities lead to the disruption of cell cycle arrest pathways, including the p53, p16, retinoblastoma (Rb), and phosphatase and tensin homologue (PTEN) tumor suppressor genes (Sidransky et al, 1992;Bolger et al, 1995b;Goussia et al, 2000;Sallinen et al, 2000). Although the human caveolin-1 gene is localized to a suspected tumor suppressor locus, 7q31.1 Fra et al, 1999;Hurlstone et al, 1999), chromosome 7 is frequently amplified, rather than deleted, in brain gliomas (Goussia et al, 2000;Holland, 2001). Thus, caveolin-1 mRNA and protein expression in rat and human astroglioma cell lines is in accordance with the frequent amplification of chromosome 7 in brain gliomas.…”

Section: Discussionmentioning

confidence: 99%

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Caveolin‐1 expression is maintained in rat and human astroglioma cell lines

Cameron

Liu

Smart

et al. 2002

Glia

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Caveolin-1 is the principal structural and functional component of caveolae, a plasmalemmal compartment that has been proposed to sequester lipid and protein components that participate in transmembrane signal transduction processes. Multiple studies reveal a reduction in the expression level of caveolin-1 mRNA and protein in many carcinomas as well as transformed cells. The human caveolin-1 gene is localized to a suspected tumor suppressor locus (7q31.1). Collectively, these data have been taken to imply that caveolin-1 may function in a tumor suppressor capacity. To determine if a reduction in the expression level of caveolin-1 mRNA and protein accompanied the transformation of astrocytes, we undertook studies of two transformed rat astroglial cell lines, C6 and DI TNC(1), as well as several cell lines derived from human glioblastoma tumors: T98G, U87MG, U118MG, U138MG, and U373MG. Ultrastructural, immunolocalization, immunoblot, and Northern blot analyses demonstrated that caveolin-1 message and protein were expressed in all rat and human glioma cells. The localization pattern, buoyant density, and detergent-insolubility property of caveolin-1 protein were indistinguishable from that determined for nontransformed type 1 astrocytes in culture. Nucleotide sequence analyses of caveolin-1 cDNAs indicate that mutations are not present in the caveolin-1 sequence in any of the glioma cell types. Taken together with previous analyses, these data indicate that, at least for astrocytes, the process of transformation in and of itself is not solely sufficient to reduce the level of caveolin-1 expression, and that caveolin-1 expression in and of itself is not solely sufficient to prevent the acquisition of a transformed phenotype.

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Section: Introductionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Caveolin‐1 expression is maintained in rat and human astroglioma cell lines

Cameron

Liu

Smart

et al. 2002

Glia

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“…Furthermore, caveolin-1 gene knockout results in increased sensitivity to oncogenic and carcinogenic stimuli (Capozza et al, 2003;Williams et al, 2003). The chromosomal location of human caveolin-1 is in a locus (7q31.1/D7S522) that is deleted in several forms of cancer Fra et al, 1999). Together, these data indicate that caveolin-1 is a growth-inhibitory protein and have led to the suggestion that caveolin-1 may act as a tumor-suppressor protein (Razani et al, 2001b).…”

Section: Introductionmentioning

confidence: 99%

Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling

et al. 2004

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“…In contrast, caveolin-1 mRNA and protein levels are strongly reduced in oncogenically transformed cells (Koleske et al, 1995;Engelman et al, 1998b) and in many (but not all) human cancer cells (Lee et al, 1998;Hurlstone et al, 1999;Racine et al, 1999;Bagnoli et al, 2000;Bender et al, 2000;Wiechen et al, 2001). This downregulation is caused by deletions within the CAV1/ CAV2 locus (Engelman et al, 1998c;Fra et al, 1999) or by silencing of the CAV1 promoter (Engelman et al, 1999a). Mitogenic signaling pathways negatively regulate transcription of the caveolin-1 and -2 genes (Engelman et al, 1999b).…”

Section: Introductionmentioning

confidence: 99%

“…Several transcription factors including a complex of E2F/DP-1, SP-1 and p53 (Bist et al, 2000;Razani et al, 2000), c-Myc (Park et al, 2001) and sterol-regulatory element binding protein (Bist et al, 1997) mediate downregulation of the caveolin-1 promoter. However, the detailed organization of the CAV1 and CAV2 promoters has not been fully elucidated (Engelman et al, 1999a;Fra et al, 1999). There is little evidence for transcription factors that positively regulate caveolin-1 or -2 expression.…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor-γ upregulates caveolin-1 and caveolin-2 expression in human carcinoma cells

2003

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Peroxisome proliferator-activated receptor-c (PPARc) is a nuclear receptor for eicosanoids that promotes differentiation of human epithelial and mesenchymal cells in vitro and in vivo. PPARc was proposed as a target for drug-induced differentiation therapy of cancer. Caveolin-1 is a constituent of plasma membrane caveolae in epithelial cells that is often downregulated upon oncogenic transformation. Caveolin-1 has growth-inhibitory activities and its disruption is sufficient to induce transformation in fibroblasts. Herein we have tested the hypothesis that caveolins are transcriptional target genes for PPARc. In human HT-29 colon carcinoma cells, thiazolidinedione PPARc ligands increased the levels of caveolin-1 and caveolin-2 proteins two to fivefold in a concentrationdependent manner within 24 h. In human MCF-7 breast adenocarcinoma cells, nonthiazolidinedione PPARc ligands elevated caveolin-2 protein three to fourfold, while the thiazoli-dinediones were less effective. Caveolin-1 mRNA levels were found to be upregulated by PPARc ligands already after 3 h in both the cell lines. Ectopic expression of a dominant-negative PPARc construct attenuated ligand-induced upregulation of caveolins in both HT-29 and HEK-293T cells, indicating that ligand action is mediated by PPARc. Ligand-treated MCF-7 cells exhibited a differentiated phenotype, as evinced by analysis of cell-specific differentiation markers: protein levels of maspin were elevated and perinuclear lipid droplets accumulated. In contrast, in HT-29 cells, caveolin expression was not correlated with differentiation. Interestingly, PPARc partially cofractionated in lipid rafts and could be coimmunoprecipitated from cell lysates with caveolin-1, indicating that PPARc and caveolin-1 may coexist in a complex. Our data indicate that PPARc participates in the regulation of caveolin gene expression in human carcinoma cells and suggest that caveolin-1 may mediate some of the phenotypic changes induced by this nuclear receptor in cancer cells. These findings may have potentially important functional implications in the context of cancer differentiation therapy and multidrug resistance.

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Human Caveolin-1 and Caveolin-2 Are Closely Linked Genes Colocalized with WI-5336 in a Region of 7q31 Frequently Deleted in Tumors

Cited by 23 publications

References 6 publications

Caveolin‐1 expression is maintained in rat and human astroglioma cell lines

Caveolin‐1 expression is maintained in rat and human astroglioma cell lines

Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling

Peroxisome proliferator-activated receptor-γ upregulates caveolin-1 and caveolin-2 expression in human carcinoma cells

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