Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors

Fink, Jason; LeBien, Tucker W.

doi:10.1016/s0301-472x(01)00619-1

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…Cyclin D1 is not expressed physiologically in the B cell lineage including the more differentiated plasma cells. On the contrary, cyclin D2 and cyclin D3 are ubiquitously expressed in normal B cells and in MM 42, 43. Cyclin D3 possesses the same functions than cyclin D1 as cell cycle regulatory molecules and p27 Kip1 is the CKI promoting growth arrest in B‐cells 44.…”

Section: Discussionmentioning

confidence: 99%

Pure antiestrogen‐induced G1‐arrest in myeloma cells results from the reduced kinase activity of cyclin D3/CDK6 complexes whereas apoptosis is mediated by endoplasmic reticulum‐dependent caspases

Gauduchon

Seguin

Marsaud

et al. 2008

Intl Journal of Cancer

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Multiple myeloma (MM) is a malignancy characterized by the accumulation of tumoral plasma cells in bone marrow. This disease remains incurable and the development of new therapeutic strategies is urgently required. We have studied the effects of 2 selective estrogen receptor disrupters (SERDs), RU 58668 (RU) and ICI 182,780 (ICI) or pure antiestrogens (AEs) on MM cell lines. Both compounds have antimyeloma activity through either cell cycle arrest or induction of apoptosis. To analyze the molecular mechanisms of SERD action, we choose 2 differently responding cell lines as models. In LP-1 cells, RU blocked cell cycle at the G1 phase. RU treatment induced a rapid decrease of c-Myc, an upregulation of p27 Kip1 , and the subsequent decreased activity of cyclin-dependent kinase, CDK6 and associated cyclin D3, impairing the inactivation of the retinoblastoma protein (pRb). In RPMI 8226 cells, RU induced apoptosis by recruiting endoplasmic reticulum-as well as mitochondria-associated caspases. Moreover, RU interfered with the NF-jB survival pathway, often deregulated in MM malignancy. Antimyeloma activities were observed in dexamethasone (Dex)-and RU-resistant cells when RU was combined with bortezomib; Dex and bortezomib being frequently used in MM therapy. RU induced the death of CD1381 cells purified from MM patients but not CD191 normal cells obtained from tonsils. Therefore, RU mediates the inhibition of survival, the activation of apoptosis and finally potentiates anticancer drug. Those combinatory effects provide a basis for the potential use of pure AEs in MM treatment. ' 2008 Wiley-Liss, Inc.Key words: multiple myeloma; pure antiestrogen; apoptosis; antiestrogenic therapy; survival pathway Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal tumor cells in the bone marrow. This accumulation of malignant plasma cells that synthesize immunoglobulins causes hyperproteinemia, renal dysfunction, bone lesions and immunodeficiency. 1 This disease, which accounts for 2% of all cancer deaths per year and nearly 20% of deaths caused by hematological malignancies in the western world, remains largely incurable despite novel therapeutic approaches targeting both myeloma cells and bone marrow environment. 2,3 Selective estrogen receptor modulators (SERMs) and selective estrogen receptors disruptors (SERDs) or pure antiestrogens (AEs) may provide a new strategy in myeloma therapy. MM cell lines and primary cells express estrogen receptors (ERs). This has been described 20 years ago using binding assays 4,5 and more recently using western blotting. 6 We and others have previously reported that SERMs inhibited cell proliferation and induced apoptosis in MM cells. [6][7][8][9] Using several MM cell lines, we demonstrated that 4-hydroxytamoxifen (4-HT) inhibits proliferation through 2 independent but concomitant processes: a block at the G0/G1-phase and the triggering of a mitochondrial death pathway. We further investigated the effects of 2 steroid-like pure AEs, RU 58668 (RU) and ICI 182...

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Section: Discussionmentioning

confidence: 99%

Pure antiestrogen‐induced G1‐arrest in myeloma cells results from the reduced kinase activity of cyclin D3/CDK6 complexes whereas apoptosis is mediated by endoplasmic reticulum‐dependent caspases

Gauduchon

Seguin

Marsaud

et al. 2008

Intl Journal of Cancer

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“…The sense/antisense primers for the murine p16 were 5 ¶-ATGGAGTCCGCTGCAGACAG-3 ¶ and 5 ¶-TGCTTG-AGCTGAAGCTATGC-3 ¶, respectively. The sense/antisense primer sequences for p16, p15, p18, p19, Cdk4, Cdk6, RB, and GAPDH were reported previously (11,20).…”

Section: Methodsmentioning

confidence: 99%

Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines

Kondo¹,

Tanaka²,

Miyake³

et al. 2008

Molecular Cancer Therapeutics

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Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. Here, we examine growth suppression efficiency of human glioblastomas by dualpeptide targeting.

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“…The sense/antisense primer sequences for p16 INK4a , Cdk4, Cdk6, CyclinD1, RB and GAPDH were as described previously 20,26 . p16INK4a: sense primer; 5′-ATGGAGCCGGCGGCGGGGAG-3′, antisense primer; 5′-TCAATCGGGGATGTCTGAGG-3′ Cdk4: sense primer; 5′-TGACAA GTGGTGGAACAGTC-3′, antisense primer; 5′-TAAGAGTGCTGCAGAGC TCG-3′ Cdk6: sense primer; 5′-TCTTGCTCCAGTCCAGCTAC-3′, antisense primer; 5′-AGCAATCCTCCACAGCTCTG-3′ CyclinD1: sense primer; 5′-GAGGAACAGAAGTGCGAGGA-3′, antisense primer; 5′-TCTGGAGAGGAAGCGTGTGA-3′ RB: sense primer; 5′-CTTGCAT GGCTCTCAGAT-3′, antisense primer; 5′-AGATTAAGAGGACAAGCA-3′ GAPDH: sense primer; 5′-GGTGAAGGTCGGAGTCAACGGA-3′, antisense primer; 5′-GAGGGATCTCGCTCCTGGAAGA-3′ Primers for M160 (α-form of CD163L1): sense 5′-AGATGCTGCTGTCATCAGAACCTT-3′, antisense 5′-TTT GCACACGACAGTTGAGGCAGTA-3′.…”

Section: Rt-pcrmentioning

confidence: 99%

Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems

et al. 2012

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Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors

Cited by 14 publications

References 34 publications

Pure antiestrogen‐induced G1‐arrest in myeloma cells results from the reduced kinase activity of cyclin D3/CDK6 complexes whereas apoptosis is mediated by endoplasmic reticulum‐dependent caspases

Pure antiestrogen‐induced G1‐arrest in myeloma cells results from the reduced kinase activity of cyclin D3/CDK6 complexes whereas apoptosis is mediated by endoplasmic reticulum‐dependent caspases

Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines

Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems

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