uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Adenovirus-mediated overexpression of p15INK4B inhibits human glioma cellgrowth, induces replicative senescence, and inhibits telomerase activitysimilarly to p16INK4A
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Show others and affiliations
2000 (English)In: Cell growth & differentiation, ISSN 1044-9523, Vol. 11, no 7, 373-384 p.Article in journal (Refereed) Published
Abstract [en]

The genes encoding the cyclin-dependent kinase inhibitors p16INK4A (CDKN2A) and p15INK4B (CDKN2B) are frequently homozygously deleted in a variety of tumor cell lines and primary tumors, including glioblastomas in which 40-50% of primary tumors display homozygous deletions of these two loci. Although the role of p16 as a tumor suppressor has been well documented, it has remained less well studied whether p15 plays a similar growth-suppressing role. Here, we have used replication-defective recombinant adenoviruses to compare the effects of expressing wild-type p16 and p15 in glioma cell lines. After infection, high levels of p16 and p15 were observed in two human glioma cell lines (U251 MG and U373 MG). Both inhibitors were found in complex with CDK4 and CDK6. Expression of p16 and p15 had indistinguishable effects on U251 MG, which has homozygous deletion of CDKN2A and CDKN2B, but a wild-type retinoblastoma (RB) gene. Cells were growth-arrested, showed no increased apoptosis, and displayed a markedly altered cellular morphology and repression of telomerase activity. Transduced cells became enlarged and flattened and expressed senescence-associated beta-galactosidase, thus fulfilling criteria for replicative senescence. In contrast, the growth and morphology of U373 MG, which expresses p16 and p15 endogenously, but undetectable levels of RB protein, were not affected by exogenous overexpression of either inhibitor. Thus, we conclude that overexpression of p15 has a similar ability to inhibit cell proliferation, to cause replicative senescence, and to inhibit telomerase activity as p16 in glioma cells with an intact RB protein pathway.

Place, publisher, year, edition, pages
2000. Vol. 11, no 7, 373-384 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-52393PubMedID: 10939591OAI: oai:DiVA.org:uu-52393DiVA: diva2:80302
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-07-01Bibliographically approved

Open Access in DiVA

No full text


Search in DiVA

By author/editor
Akusjärvi, Göran
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Cell growth & differentiation
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 258 hits
ReferencesLink to record
Permanent link

Direct link