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rdf:type |
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lifeskim:mentions |
umls-concept:C0021758,
umls-concept:C0040845,
umls-concept:C0205263,
umls-concept:C0334094,
umls-concept:C0334634,
umls-concept:C0871261,
umls-concept:C1539081,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1879547,
umls-concept:C2911692
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pubmed:issue |
2
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pubmed:dateCreated |
2005-2-7
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pubmed:abstractText |
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with poor response to therapy and unfavorable prognosis. Here, we show that retinoic acid (RA) isomers significantly inhibit the proliferation of both primary MCL cultures (n = 7) and established cell lines (Granta 519 and SP-53) as shown by [(3)H]thymidine uptake and carboxyfluorescein diacetate succinimidyl ester labeling coupled with cyclin D1 staining. RA induces cell accumulation in G(0)-G(1) together with a marked up-regulation of p27(Kip1) by inhibiting ubiquitination and proteasome-dependent degradation of the protein. The p21(Cip1) inhibitor was also up-regulated by RA in Granta 519 cells, whereas the expression of cyclin D1 is unaffected. Most of RA-induced p27(Kip1) was bound to cyclin D1/cyclin-dependent kinase 4 complexes, probably contributing to the decreased cyclin-dependent kinase 4 kinase activity and pRb hypophosphorylation observed in RA-treated cells. Experiments with receptor-selective ligands indicate that RA receptor alpha cooperates with retinoid X receptors in mediating RA-dependent MCL cell growth inhibition. Notably, RA isomers, and particularly 9-cis-RA, also inhibited the growth-promoting effect induced in primary MCL cells by CD40 activation alone or in combination with interleukin-4. Immunohistochemical analysis showed that significant numbers of CD40L-expressing lymphoid cells are present in lymph node biopsies of MCL patients. These results therefore further strengthen the possibility that triggering of CD40 by infiltrating CD40L+ cells may continuously promote the growth of MCL cells in vivo. On these grounds, our findings that RA inhibits basal MCL proliferation as well as MCL growth-promoting effects exerted by microenvironmental factors make these compounds highly attractive in terms of potential clinical efficacy in this setting.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/CDK4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0008-5472
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pubmed:author |
pubmed-author:BoiocchiMauroM,
pubmed-author:BononiAntonioA,
pubmed-author:CarboneAntoninoA,
pubmed-author:CariatiRobertaR,
pubmed-author:CuneoAntonioA,
pubmed-author:Dal ColJessicaJ,
pubmed-author:DoglioniClaudioC,
pubmed-author:DolcettiRiccardoR,
pubmed-author:GloghiniAnnunziataA,
pubmed-author:GuidoboniMassimoM,
pubmed-author:MaestroRobertaR,
pubmed-author:PavanAlessandroA,
pubmed-author:PomponiFabrizioF,
pubmed-author:RizzoSilvanaS,
pubmed-author:SpinaMicheleM,
pubmed-author:ZancaiPaolaP
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
587-95
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15695403-Aged,
pubmed-meshheading:15695403-Antigens, CD40,
pubmed-meshheading:15695403-CD40 Ligand,
pubmed-meshheading:15695403-Cell Cycle Proteins,
pubmed-meshheading:15695403-Cell Proliferation,
pubmed-meshheading:15695403-Cell Survival,
pubmed-meshheading:15695403-Cyclin D1,
pubmed-meshheading:15695403-Cyclin-Dependent Kinase 4,
pubmed-meshheading:15695403-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15695403-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:15695403-Cyclin-Dependent Kinases,
pubmed-meshheading:15695403-Female,
pubmed-meshheading:15695403-Humans,
pubmed-meshheading:15695403-Interleukin-4,
pubmed-meshheading:15695403-Lymphoma, Mantle-Cell,
pubmed-meshheading:15695403-Male,
pubmed-meshheading:15695403-Middle Aged,
pubmed-meshheading:15695403-Proteasome Endopeptidase Complex,
pubmed-meshheading:15695403-Proto-Oncogene Proteins,
pubmed-meshheading:15695403-Receptors, Retinoic Acid,
pubmed-meshheading:15695403-Tretinoin,
pubmed-meshheading:15695403-Tumor Suppressor Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
Retinoic acid inhibits the proliferative response induced by CD40 activation and interleukin-4 in mantle cell lymphoma.
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pubmed:affiliation |
Immunovirology and Biotherapy Unit, Department of Pre-Clinical and Epidemiological Research, IRCCS-National Cancer Institute, Aviano (PN), Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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