Linked Life Data

11840272

Source:http://linkedlifedata.com/resource/pubmed/id/11840272

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pubmed-article:11840272pubmed:abstractTextMultiple myeloma (MM) is a clonal neoplasm of plasma cells which offers an excellent model to study multistep molecular oncogenesis. In 20-25% of primary tumors and cell lines examined, cyclin D1 is overexpressed due to the translocation t(11;14)(q13;q32). We have characterized cyclin-dependent kinase inhibitor p15 (CDKN2B), p16 (CDKN2A) and p18 (CDKN2C) deletions in cyclin D1-expressing and non-expressing MM cell lines. p18 was found to be frequently deleted (38%); in some cases p18 deletions coexisted with hemizygous p16 deletion. To examine the function of p18 as a putative tumor suppressor in myeloma cells, a zinc-inducible p18 construct was stably transfected into KMS12, a MM cell line with biallelic p18 and monoallelic p16 deletions as well as cyclin D1 overexpression. Ectopic expression of p18 caused 40-45% growth suppression as determined by trypan blue exclusion and MTS assays. p18 induction also resulted in apoptosis, suggesting that inhibition of the cyclin D1/CDK/pRb pathway in these tumor cells could be a crucial step toward the induction of tumor regression via apoptotic cell death. This cell cycle pathway is thus frequently mutated and provides a potentially novel target for gene therapeutic or pharmacologic approaches to human myeloma.lld:pubmed
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pubmed-article:11840272pubmed:articleTitleFrequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis.lld:pubmed
pubmed-article:11840272pubmed:affiliationDepartment of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.lld:pubmed
pubmed-article:11840272pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11840272pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:11840272pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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