Proteomic analysis of mantle-cell lymphoma by protein microarray

Ghobrial, Irène M.; McCormick, Daniel J.; Kaufmann, Scott H.; Leontovich, Alexey A.; Loegering, David A.; Dai, Nga T.; Krajnik, Kelly L.; Stenson, Mary; Melhem, Mona F.; Novak, Anne J.; Ansell, Stephen M.; Witzig, Thomas E.

doi:10.1182/blood-2004-10-3999

Cited by 128 publications

(85 citation statements)

References 32 publications

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“…In rats, PPP5C mRNA levels markedly increased in malignant ascites hepatomas (46). Furthermore, a protein microarray analysis of mantle-cell lymphoma also revealed elevated PPP5C expression (47). With regards to PC, increased PPP5C expression was observed in PANC-1 cells treated with GEM in the present study.…”

Section: Discussionsupporting

confidence: 61%

Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cells inï¿½vitro

Zhu

et al. 2018

Oncol Lett

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Abstract. The targeting protein of serine/threonine protein phosphatase 5 (PPP5C) has been reported to be present in various malignancies. However, its functional role in pancreatic cancer (PC) remains unknown. In the present study, the function of PPP5C in PC cells treated with the first-line drug gemcitabine (GEM) was investigated. Short hairpin (sh)RNA targeting PPP5C was constructed to knockdown PPP5C in PANC-1 cells. Cell cycle and apoptosis analyses were performed in order to investigate the mechanisms underlying the effects induced by PPP5C silencing combined with GEM treatment. Western blot analysis was applied to detect the expression of certain key regulators of cell apoptosis in PANC-1 cells treated with GEM. shRNA against PPP5C effectively suppressed the proliferation of PANC-1 cells treated with GEM. Additionally, cell cycle analysis indicated that PPP5C knockdown resulted in a higher number of PANC-1 cells treated with GEM in G 0 /G 1 phase arrest. Knockdown of PPP5C increased the expression of associated apoptotic markers, including cleaved caspase 3, poly (ADP-ribose) polymerase and phosphorylated (p)-p53. In addition, the combination of treatment with GEM and PPP5C silencing significantly increased the apoptosis of PANC-1 cells by affecting the expression levels of p-c-Jun N-terminal kinases and p-p38. The present study suggests that PPP5C may be a potential target for the treatment of PC and that it may enhance the gemcitabine sensitivity of PC cells.

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Section: Discussionsupporting

confidence: 61%

Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cells inï¿½vitro

Zhu

et al. 2018

Oncol Lett

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“…48 In addition, our data confirm recent gene and protein expression studies of MCL that showed overexpression of AKT pathway components. 49,50 With the exception of activated p70S6K, all of the other mTOR pathway molecules were detected primarily in the cytoplasm of MCL cells. Notably, localization of mTOR and its activated form has been reported predominantly in the cytoplasm or the nucleus, depending on the cell type and conditions, and it seems to be shuttled between the two compartments with yet unknown functional consequences.…”

Section: Discussionmentioning

confidence: 99%

Activation of Mammalian Target of Rapamycin Signaling Promotes Cell Cycle Progression and Protects Cells from Apoptosis in Mantle Cell Lymphoma

Peponi

Δράκος

Reyes

et al. 2006

The American Journal of Pathology

111

108

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Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473 p-AKT, 13 of 21 (62%) Ser2448 p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

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“…As many as half of all human and murine lymphomas overexpress Mdm2 protein, including lymphomas that have inactivated the tumor suppressor p53 or p14/p19 ARF (Watanabe et al, 1996;Eischen et al, 1999;Alt et al, 2003;Wilda et al, 2004;Ghobrial et al, 2005). Mdm2 is an essential intermediary in the ARFp53 tumor suppressor pathway.…”

Section: Introductionmentioning

confidence: 99%

Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells

et al. 2007

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Mdm2, a regulator of the p53 tumor suppressor, is frequently overexpressed in lymphomas, including lymphomas that have inactivated p53. However, the biological consequences of Mdm2 overexpression in lymphocytes are not fully resolved. Here, we report that increased expression of Mdm2 in B cells augmented proliferation and reduced susceptibility to p53-dependent apoptosis, which was due to inhibition of p53 and suppression of p21 expression. Notably, developing and mature B cells from Mdm2 transgenic mice had an increased frequency of chromosomal/chromatid breaks and/or aneuploidy. This Mdm2-mediated genome instability occurred at a similar frequency as that in B cells overexpressing the oncogene c-Myc, but the chromosomal instability was not further enhanced when Mdm2 and c-Myc were overexpressed together. Elevated Mdm2 expression alone increased the occurrence of B-cell transformation in vivo and cooperated with c-Myc overexpression, resulting in an acceleration of B-cell lymphomagenesis. In addition, the frequency of p53 mutations was reduced, but not eliminated, in lymphomas arising in Mdm2/Emu-myc double transgenic mice. Therefore, increased Mdm2 expression facilitated B-cell lymphomagenesis, in part, through regulation of p53 by altering B-cell proliferation and susceptibility to apoptosis, and by inducing chromosomal instability

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Proteomic analysis of mantle-cell lymphoma by protein microarray

Abstract: Mantle-cell lymphoma (MCL) is

Cited by 128 publications

References 32 publications

Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cells inï¿½vitro

Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cells inï¿½vitro

Activation of Mammalian Target of Rapamycin Signaling Promotes Cell Cycle Progression and Protects Cells from Apoptosis in Mantle Cell Lymphoma

Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells

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