Molecular events associated with arsenic-induced malignant transformation of human prostatic epithelial cells: aberrant genomic DNA methylation and K-ras oncogene activation

Benbrahim‐Tallaa, Lamia; Waterland, Robert A.; Stýblo, Miroslav; Achanzar, William E.; Webber, Mukta M.; Waalkes, Michael P.

doi:10.1016/j.taap.2004.11.017

Cited by 159 publications

(154 citation statements)

References 49 publications

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“…RAC1 and FGFR3 were evaluated in previous studies (Kwabi-Addo et al, 2001;Gowardhan et al, 2005;Chaffer et al, 2007;, but here we report PIK3C2B gene down-regulation and its relationship to PCA for the first time.Two important gene members of this pathway were down-regulated. K-RAS is not only an oncogene, but also a known target in differentiation therapy of PCA (Benbrahim-Tallaa et al, 2005. ERBB2 overexpression is important in PCA and our finding is in concordance with previous observations (Liu et al, 2001;Calvo et al, 2003;Ullén et al, 2005).…”

Section: Discussionsupporting

confidence: 93%

Gene network and canonical pathway analysis in prostate cancer: a microarray study

et al. 2008

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The molecular mechanism playing a role in the development of prostate cancer (PCA) is not well defined. We decided to determine the changes in gene expression in PCA tissues and to compare them to those in noncancerous samples. Prostate tissue samples were collected by needle biopsy from 21 PCA and 10 benign prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined by microarray method. In the progression to PCA, 738 up-regulated and 515 downregulated genes were detected in samples. Analysis using Ingenuity Pathway Analysis (IPA) software revealed that 466 network and 423 functions-pathways eligible genes were up-regulated, and 363 network and 342 functions-pathways eligible genes were down-regulated. Up-regulated networks were identified around IL-1β and insulin-like growth factor-1 (IGF-1) genes. The NFKB gene was centered around two upand down-regulated networks. Up-regulated canonical pathways were assigned and four of them were evaluated in detail: acute phase response, hepatic fibrosis, actin cytoskeleton, and coagulation pathways.Axonal guidance signaling was the most significant down-regulated canonical pathway. Our data provide not only networks between the genes for understanding the biologic properties of PCA but also useful pathway maps for future understanding of disease and the construction of new therapeutic targets.

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Section: Discussionsupporting

confidence: 93%

Gene network and canonical pathway analysis in prostate cancer: a microarray study

et al. 2008

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“…Aberrant expressed genes can be classified into many categories such as stress response genes, hormone-related genes, cytokines, apoptotic genes, cell cycle regulatory genes, proteolytic genes, and proto-oncogenes (Kitchin, 2001;Yih et al, 2002;Zheng et al, 2003;Chen et al, 2004). In particular, genes important in controlling cell proliferation and transformation are aberrantly expressed during the arsenic-induce carcinogenesis (Shimizu et al, 1998;Chen et al, 2001;Hamadeh et al, 2002;Li et al, 2003;Liu et al, 2004;Benbrahim-Tallaa et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1–Cul3 interaction

Wang

Sun

Chen

et al. 2008

Toxicology and Applied Pharmacology

127

101

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Drinking water contaminated with arsenic, a human carcinogen, is a worldwide health issue. An understanding of cellular signaling events in response to arsenic exposure and rational designing of strategies to reduce arsenic damages by modulating signaling events are important to fight against arsenic-induced diseases. Previously, we reported that activation of the Nrf2-mediated cellular defense pathway confers protection against toxic effects induced by sodium arsenite [As(III)] or monomethylarsonous acid [MMA(III)]. Paradoxically, arsenic has been reported to induce the Nrf2-dependent signaling pathway. Here, we report the unique mechanism of Nrf2 induction by arsenic. Similar to tert-butylhydroquinone (tBHQ) or sulforaphane (SF), arsenic induced the Nrf2-dependent response through enhancing Nrf2 protein levels by inhibiting Nrf2 ubiquitination and degradation. However, the detailed action of arsenic in Nrf2 induction is different from that of tBHQ or SF. Arsenic markedly enhanced the interaction between Keap1 and Cul3, subunits of the E3 ubiquitin ligase for Nrf2, which led to impaired dynamic assembly/disassembly of the E3 ubiquitin ligase and thus decreased its ligase activity. Furthermore, induction of Nrf2 by arsenic is independent of the previously identified C151 residue in Keap1 that is required for Nrf2 activation by tBHQ or SF. Distinct mechanisms of Nrf2 activation by seemingly harmful and beneficial reagents provide a molecular basis to design Nrf2-activating agents for therapeutic intervention.

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“…Chronic exposure of arsenic contributes to an increased risk of skin, lung, bladder, liver, and kidney cancers (1). Current studies suggest that long-term and lowdose exposure to arsenic is involved in an increased rate of malignant transformation of human keratinocyte HaCaT cells (2)(3), human small airway epithelial cells (4), human prostate epithelial cells (5)(6), mouse epidermal JB6 Cl41 cells (7), and rat liver epithelial TRL1215 cells (8). Although arsenic causes carcinogenesis in humans, the mechanism explaining the effect of chronic arsenic exposure in tumor development is still undefined.…”

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confidence: 99%

Polycomb (PcG) Proteins, BMI1 and SUZ12, Regulate Arsenic-induced Cell Transformation

Kim

et al. 2012

Journal of Biological Chemistry

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Molecular events associated with arsenic-induced malignant transformation of human prostatic epithelial cells: aberrant genomic DNA methylation and K-ras oncogene activation

Cited by 159 publications

References 49 publications

Gene network and canonical pathway analysis in prostate cancer: a microarray study

Gene network and canonical pathway analysis in prostate cancer: a microarray study

Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1–Cul3 interaction

Polycomb (PcG) Proteins, BMI1 and SUZ12, Regulate Arsenic-induced Cell Transformation

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