SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Persson Anders) ;spr:eng;pers:(Wegiel Barbara)"

Sökning: WFRF:(Persson Anders) > Engelska > Wegiel Barbara

  • Resultat 1-7 av 7
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Wegiel, Barbara, et al. (författare)
  • A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer
  • 2005
  • Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 24:42, s. 6385-6393
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated levels of cyclin A1 expression have been implicated in acute myeloid leukemia and in male germ cell tumors. However, a role of cyclin A1 in tumorigenesis of prostate cancer has not been reported. In the present study, expression of cyclin A1 in patients with prostate cancer and a role of cyclin A1 in mediating expression of vascular endothelial growth factor (VEGF) were investigated. Cyclin A1 was highly expressed in aggressive tumors and was significantly correlated with VEGF expression in 96 patients with prostate cancer. Treatment of LNCaP cells with R1881, a synthetic androgen resulted in increased cyclin A1 expression. Induction of cyclin A1 expression in LNCaP cells led to an increase in VEGF expression and this effect was manifested upon the R1881 treatment. Cyclin A1 failed to mediate VEGF activation in DU-145 cells lacking a functional Rb and an androgen receptor (AR). Although AR expression was induced into DU-145 cells, cyclin A1 was unable to mediate VEGF expression. However, induced coexpression of cyclin A1, Rb and AR in DU-145 cells in the presence of R1881 greatly promoted VEGF promoter activity. This suggests that cyclin A1 mediates VEGF expression in cooperation with Rb- and androgen-dependent pathways in prostate cancer.
  •  
2.
  • Wegiel, Barbara, et al. (författare)
  • Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth
  • 2013
  • Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 73:23, s. 7009-7021
  • Tidskriftsartikel (refereegranskat)abstract
    • One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype. Carbon monoxide (CO), one of the products of the cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been implicated in carcinogenesis and therapeutic resistance. However, the functional contributions of CO and HO-1 to these processes are poorly defined. In human prostate cancers, we found that HO-1 was nuclear localized in malignant cells, with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy, with growth arrest and apoptosis induced in vivo in part through mitotic catastrophe. CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation, and mitochondrial collapse. Collectively, our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics, ultimately resulting in metabolic exhaustion.
  •  
3.
  • Wegiel, Barbara, et al. (författare)
  • Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cells via MAPK/Erk and androgen receptor pathways
  • 2009
  • Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001) and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (r(s) (2) = -0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis.
  •  
4.
  • Wegiel, Barbara, et al. (författare)
  • Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival
  • 2008
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 122:7, s. 1521-1529
  • Tidskriftsartikel (refereegranskat)abstract
    • Interleukin-6 (IL6) is a growth and survival factor in human prostate cancer (PCa) cells with aggressive phenotypes and has been implicated in the progression of hormone refractory PCas. In the present study, we characterized the IL6-triggered PI3K/Akt and MAPK/Erk signaling. We identified the A-type cyclin, cyclin A1 as an important downstream target of PI3K/Akt. Treatment of cells with PI3K inhibitor or cotransfection with a vector expressing wild-type PTEN decreased cyclin A1 promoter activity. Cyclin A1 promoter activity and its expression were upregulated by constitutively active myristoylated Akt and were downregulated by dominant negative Akt in response to IL6 stimulation. LNCaP cells overexpressing cyclin A1 are resistant to camptothecin-induced apoptosis. Conversely, targeted knockdown of cyclin A1 via shRNA in LNCaP IL6+ cells resulted in decreased survival after treatment with camptothecin. This suggests that cyclin A1 is an important downstream target of PI3K/Akt that transduces survival signals in response to IL6 stimulation. Xenograft tumors generated from LNCaP-IL6+ cells expressing IL6 had higher levels of cyclin A1 and had rapid tumor growth compared to LNCaP xenograft tumors. Taken together, IL6 might utilize PI3K/Akt and cyclin A1 to promote tumor cell survival in PCa. (c) 2007 Wiley-Liss, Inc.
  •  
5.
  • Wegiel, Barbara, et al. (författare)
  • Molecular Pathways in the Progression of Hormone-Independent and Metastatic Prostate Cancer
  • 2010
  • Ingår i: Current Cancer Drug Targets. - 1873-5576. ; 10:4, s. 392-401
  • Forskningsöversikt (refereegranskat)abstract
    • Once prostate cancer becomes castration resistant, cancer cells may rapidly gain the ability to invade and to metastasize to lymph nodes and distant organs. The progression through hormone-dependent to hormone-independent/castration-resistant and metastatic PCa is poorly understood. In this review paper, we provide an overview on the cellular and molecular mechanisms underlying the process of tumor cell invasion and metastasis in prostate cancer. We specifically presented the most recent findings on the role of multiple cellular signaling pathways including androgen receptor (AR), mitogen-activated protein kinases (MAPK), Akt, transforming growth factor beta (TGF beta), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in the development of hormone-independent/castration-resistant prostate cancer. In addition, we also discussed the recent findings on signatures of gene expression during prostate cancer progression. Our overviews on the novel findings will help to gain better understanding of the complexity of molecular mechanisms that may play an essential role for the development of castration-resistant and metastatic prostate cancer. It will also shed light on the identifying specific targets and design effective therapeutic drug candidates.
  •  
6.
  •  
7.
  • Wegiel, Barbara, et al. (författare)
  • Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and metastasis
  • 2008
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:14, s. 1022-1036
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cyclin A1 is a cell cycle regulator that has been implicated in the progression of prostate cancer. Its role in invasion and metastasis of this disease has not been characterized.METHODS: Immunohistochemistry and cDNA microarray analyses were used to assess protein and mRNA expression of cyclin A1 and proteins with roles in metastasis, including vascular endothelial growth factor (VEGF), metalloproteinase 2 (MMP2), and MMP9, in human prostate cancer. Transient transfection and infection with viral vectors expressing cyclin A1 and short hairpin RNA (shRNA) targeting cyclin A1 were used to study the effects of altered cyclin A1 expression in PC3 prostate cancer cells. The BrdU assay, annexin V staining, and invasion chambers were used to examine cyclin A1 effects on proliferation, apoptosis, and invasion, respectively. The role of cyclin A1 and androgen receptor (AR) in transcription of VEGF and MMP2 was assessed by promoter mutation and chromatin immunoprecipitation. The effect of cyclin A1 expression on tumor growth and metastasis was analyzed in a mouse model of metastasis. All statistical tests were two-sided.RESULTS: Cyclin A1 protein and mRNA expression were statistically significantly higher in prostate cancers than in adjacent benign tissues. A statistically significant correlation between expression of cyclin A1 and of MMP2, MMP9, and VEGF was observed in prostate tumors from 482 patients (P values from Spearman rank correlation tests < .001). PC3 cells that overexpressed cyclin A1 showed increased invasiveness, and inhibition of cyclin A1 expression via shRNA expression reduced invasiveness of these cells. Eight of 10 mice (80%) bearing PC3 cells overexpressing cyclin A1 had infiltration of tumor cells in lymph node, liver, and lung, but all 10 mice bearing tumors expressing control vector were free of liver and lung metastases and only one mouse from this group had lymph node metastasis (P values from Fisher exact tests < .001). Cyclin A1, in concert with AR, bound to and increased expression from the VEGF and MMP2 promoters.CONCLUSIONS: Cyclin A1 contributes to prostate cancer invasion by modulating the expression of MMPs and VEGF and by interacting with AR.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-7 av 7

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy