Linked Life Data

11076533

Source:http://linkedlifedata.com/resource/pubmed/id/11076533

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2000-11-30
pubmed:abstractText
Squamous cell carcinomas of the lung and cervix arise by neoplastic transformation of their respective tissue epithelia. In the case of cervical carcinomas, an increasing body of evidence implicates the human papillomavirus, HPV (types 16 and 18), as playing a pivotal role in this malignant transformation process. The HPV early genes E6 and E7 are known to inactivate the tumor suppressors p53 and Rb, respectively; this leads to disruption of cell cycle regulation, predisposing cells to a cancerous phenotype. However, the role of caveolin-1 (a putative tumor suppressor) in this process remains unknown. Here, we show that caveolin-1 protein expression is consistently reduced in a panel of lung and cervical cancer derived cell lines and that this reduction is not due to hyperactivation of p42/44 MAP kinase (a known negative regulator of caveolin-1 transcription). Instead, we provide evidence that this down-regulation event is due to expression of the HPV E6 viral oncoprotein, as stable expression of E6 in NIH 3T3 cells is sufficient to dramatically reduce caveolin-1 protein levels. Furthermore, we demonstrate that p53-a tumor suppressor inactivated by E6-is a positive regulator of caveolin-1 gene transcription and protein expression. SiHa cells are derived from a human cervical squamous carcinoma, harbor a fully integrated copy of the HPV 16 genome (including E6), and show dramatically reduced levels of caveolin-1 expression. We show here that adenoviral-mediated gene transfer of the caveolin-1 cDNA to SiHa cells restores caveolin-1 protein expression and abrogates their anchorage-independent growth in soft agar. Taken together, our results suggest that the HPV oncoprotein E6 down-regulates caveolin-1 via inactivation of p53 and that replacement of caveolin-1 expression can partially revert HPV-mediated cell transformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13916-24
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11076533-3T3 Cells, pubmed-meshheading:11076533-Animals, pubmed-meshheading:11076533-Antiviral Agents, pubmed-meshheading:11076533-Carcinoma, Squamous Cell, pubmed-meshheading:11076533-Caveolin 1, pubmed-meshheading:11076533-Caveolins, pubmed-meshheading:11076533-Cell Line, Transformed, pubmed-meshheading:11076533-Cell Transformation, Neoplastic, pubmed-meshheading:11076533-Cell Transformation, Viral, pubmed-meshheading:11076533-Down-Regulation, pubmed-meshheading:11076533-Female, pubmed-meshheading:11076533-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11076533-Genes, p53, pubmed-meshheading:11076533-Growth Inhibitors, pubmed-meshheading:11076533-HeLa Cells, pubmed-meshheading:11076533-Humans, pubmed-meshheading:11076533-Mice, pubmed-meshheading:11076533-Mice, Inbred BALB C, pubmed-meshheading:11076533-Oncogene Proteins, Viral, pubmed-meshheading:11076533-Papillomaviridae, pubmed-meshheading:11076533-Phenotype, pubmed-meshheading:11076533-Promoter Regions, Genetic, pubmed-meshheading:11076533-Recombinant Proteins, pubmed-meshheading:11076533-Repressor Proteins, pubmed-meshheading:11076533-Transfection, pubmed-meshheading:11076533-Tumor Cells, Cultured, pubmed-meshheading:11076533-Tumor Suppressor Protein p53, pubmed-meshheading:11076533-Up-Regulation, pubmed-meshheading:11076533-Uterine Cervical Neoplasms
pubmed:year
2000
pubmed:articleTitle
Caveolin-1 expression is down-regulated in cells transformed by the human papilloma virus in a p53-dependent manner. Replacement of caveolin-1 expression suppresses HPV-mediated cell transformation.
pubmed:affiliation
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't