Oncogenic Action of Secreted Phospholipase A2 in Prostate Cancer

Sved, Paul; Scott, Kieran F.; McLeod, Duncan; King, Nicholas J. C.; Singh, Jas; Tsatralis, Tania; Nikolov, Blagoy; Boulas, John; Nallan, Laxman; Gelb, Michael H.; Sajinovic, Mila; Graham, Gerard J.; Russell, Pamela J.; Dong, Qihan

doi:10.1158/0008-5472.can-03-3018

Cited by 101 publications

(108 citation statements)

References 22 publications

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“…56,57 In line with the mitogenic function of PLA2 pathway products, inhibitors of PLA2s have been shown to block proliferation of human breast cancer-, promonocyticand prostate cancer cell lines. 33,58,59 Consistent with these reports, in vitro drug tests in our study showed that all three identified compounds inhibited proliferation and induced apoptosis in an APL cell line. Significantly, these findings highlight the potential of our drug screening strategy to identify candidate drugs with antileukemic effects that might be used as supplements in current APL treatment protocols.…”

Section: Discussionsupporting

confidence: 91%

“…The current standard regimes for APL therapy all include combinations of ATRA 33 and anthracycline-based chemotherapy. 5 Despite this, these regimens have markedly increased the rate of complete remission and the long-term outcome of APL patients, approximately 10-30% of patients will suffer from recurrent disease within a period of 5 years.…”

Section: Identification Of Candidate Drugs For the Treatment Of Aplmentioning

confidence: 99%

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A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

et al. 2010

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Chromosomal translocations of transcription factors generating fusion proteins with aberrant transcriptional activity are common in acute leukemia. In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARA) fusion protein, which emerges as a consequence of the t(15;17) translocation, acts as a transcriptional repressor that blocks neutrophil differentiation at the promyelocyte (PM) stage. In this study, we used publicly available microarray data sets and identified signatures of genes dysregulated in APL by comparison of gene expression profiles of APL cells and normal PMs representing the same stage of differentiation. We next subjected our identified APL signatures of dysregulated genes to a series of computational analyses leading to (i) the finding that APL cells show stem cell properties with respect to gene expression and transcriptional regulation, and (ii) the identification of candidate drugs and drug targets for therapeutic interventions. Significantly, our study provides a conceptual framework that can be applied to any subtype of AML and cancer in general to uncover novel information from published microarray data sets at low cost. In a broader perspective, our study provides strong evidence that genomic strategies might be used in a clinical setting to prospectively identify candidate drugs that subsequently are validated in vitro to define the most effective drug combination for individual cancer patients on a rational basis.

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Section: Discussionsupporting

confidence: 91%

Section: Identification Of Candidate Drugs For the Treatment Of Aplmentioning

confidence: 99%

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

et al. 2010

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“…In particular, the overexpression of human sPLA 2 -IIA in gastric adenocarcinoma was proposed to be related to prolonged survival and less frequent metastasis (Leung et al, 2002;Aggarwal et al, 2006). By contrast, sPLA 2 -IIA overexpression has been associated to oncogenic effects in prostate cancer (Sved et al, 2004) and is related to poor prognosis (Graff et al, 2001). The polymorphism of the sPLA 2 -IIA gene, PLA2G2A, is also associated to some phenotypic features of patients with familial adenomatous polyposis (Yanaru-Fujisawa et al, 2007).…”

mentioning

confidence: 99%

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

Wendum

Greenspan

et al. 2008

Br J Cancer

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Recent studies suggest that secreted phospholipases A 2 (sPLA 2 s) represent attractive potential tumour biomarkers and therapeutic targets for various cancers. As a first step to address this issue in human colorectal cancer, we examined the expression of the full set of sPLA 2 s in sporadic adenocarcinomas and normal matched mucosa from 21 patients by quantitative PCR and immunohistochemistry. In normal colon, PLA2G2A and PLA2G12A were expressed at high levels, PLA2G2D, PLA2G5, PLA2G10 and PLA2G12B at moderate levels, and PLA2G1B, PLA2G2F and PLA2G3 at low levels. In adenocarcinomas from left and right colon, the expression of PLA2G3 was increased by up to 40-fold, while that of PLA2G2D and PLA2G5 was decreased by up to 23-and 14-fold. The variations of expression for sPLA 2 -IID, sPLA 2 -III and sPLA 2 -V were confirmed at the protein level. The expression pattern of these sPLA 2 s appeared to be linked respectively to the overexpression of interleukin-8, defensin a6, survivin and matrilysin, and downregulation of SFRP-1 and RLPA-1, all these genes being associated to colon cancer. This original sPLA 2 profile observed in adenocarcinomas highlights the potential role of certain sPLA 2 s in colon cancer and suggests that sPLA 2 -III might be a good candidate as a novel biomarker for both left and right colon cancers.

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“…However, despite the high number of membrane proteins they obtained, none of them are high molecular weight proteins. Interestingly, adenylate kinase and phospholipase A2 were shown to be over-expressed in prostatic cancer (43,44) and the putative SHBG receptor was also first described in the prostate (1). Given the association of these proteins with SHBG in the brain it is not known at this time if these proteins are also involved in brain cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening

Gnanasekar¹

2009

Int J Mol Med

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Abstract. The present study reports the identification of human sex hormone binding globulin (SHBG)-interacting proteins in the brain using a phage display-based screening technology. Phage display is a system in which a foreign protein is displayed on the surface of a bacteriophage as a fusion protein with one of the coat proteins of the bacteriophage. T7 phage clones expressing normal human brain proteins (human normal brain phage-display cDNA expression library) were screened using SHBG as bait. The bound phage clones were then identified by DNA sequencing and by BLAST search analysis. Of the twenty binding proteins analyzed, three were found to be membrane-associated proteins: synaptosomal associated protein 25 (SNAP25), Thy-1 cell surface antigen and zonadhesin. Further studies will determine if the interactions of SHBG with these proteins have any role in the internalization and cell signaling events or whether they contribute to steroid delivery to specific cells.

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Oncogenic Action of Secreted Phospholipase A2 in Prostate Cancer

Cited by 101 publications

References 22 publications

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate

Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening

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