ArticleEnvironmental health perspectives2008
PI-3K/Akt pathway-dependent cyclin D1 expression is responsible for arsenite-induced human keratinocyte transformation.
Article in Environmental health perspectives, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 56 citations in OpenAlex.
- MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway.Molecular therapy. Nucleic acids · 2023Article
- The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.Molecular & cellular proteomics : MCP · 2023Article
- Inorganic arsenic induces sex-dependent pathological hypertrophy in the heart.American journal of physiology. Heart and circulatory physiology · 2021Article
- Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells.Frontiers in pharmacology · 2019Article
- Article
- Crucial role of c-Jun phosphorylation at Ser63/73 mediated by PHLPP protein degradation in the cheliensisin a inhibition of cell transformation.Cancer prevention research (Philadelphia, Pa.) · 2014Article
- The N-terminal region of p27 inhibits HIF-1α protein translation in ribosomal protein S6-dependent manner by regulating PHLPP-Ras-ERK-p90RSK axis.Cell death & disease · 2014Article
- Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability.Oncotarget · 2014Article
- SUMOylation of RhoGDIα is required for its repression of cyclin D1 expression and anchorage-independent growth of cancer cells.Molecular oncology · 2014Article
- Article
- Cyclin d1 downregulation contributes to anticancer effect of isorhapontigenin on human bladder cancer cells.Molecular cancer therapeutics · 2013Article
- X-linked inhibitor of apoptosis protein (XIAP) regulation of cyclin D1 protein expression and cancer cell anchorage-independent growth via its E3 ligase-mediated protein phosphatase 2A/c-Jun axis.The Journal of biological chemistry · 2013Article
- GADD45β mediates p53 protein degradation via Src/PP2A/MDM2 pathway upon arsenite treatment.Cell death & disease · 2013Article
- The role of EGFR/PI3K/Akt/cyclinD1 signaling pathway in acquired middle ear cholesteatoma.Mediators of inflammation · 2013Article
- Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B.Carcinogenesis · 2012Article
- Polycomb (PcG) proteins, BMI1 and SUZ12, regulate arsenic-induced cell transformation.The Journal of biological chemistry · 2012Article
- Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability.Toxicology and applied pharmacology · 2012Article
- Cyclooxygenase-2 (COX-2) mediates arsenite inhibition of UVB-induced cellular apoptosis in mouse epidermal Cl41 cells.Current cancer drug targets · 2012Article
- Akt activation is responsible for enhanced migratory and invasive behavior of arsenic-transformed human bronchial epithelial cells.Environmental health perspectives · 2012Article
- Activation and up-regulation of translation initiation factor 4B contribute to arsenic-induced transformation.Molecular carcinogenesis · 2011Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundLong-term exposure of arsenite leads to human skin cancer. However, the exact mechanisms of arsenite-induced human skin carcinogenesis remain to be defined.
objectivesIn this study, we investigated the potential role of PI-3K/Akt/cyclin D1in the transformation of human keratinocytic cells upon arsenite exposure.
methodsWe used the soft agar assay to evaluate the cell transformation activity of arsenite exposure and the nude mice xenograft model to determine the tumorigenesis of arsenite-induced transformed cells. We used the dominant negative mutant and gene knockdown approaches to elucidate the signaling pathway involved in this process.
resultsOur results showed that repeated long-term exposure of HaCat cells to arsenite caused cell transformation, as indicated by anchorage-independent growth in soft agar. The tumorigenicity of these transformed cells was confirmed in nude mice. Treatment of cells with arsenite also induced significant activation of PI-3K and Akt, which was responsible for the anchorage-independent cell growth induced by arsenite exposure. Furthermore, our data also indicated that cyclin D1 is an important downstream molecule involved in PI-3K/Akt-mediated cell transformation upon arsenite exposure based on the facts that inhibition of cyclin D1 expression by dominant negative mutants of PI-3K, and Akt, or the knockdown of the cyclin D1 expression by its specific siRNA in the HaCat cells resulted in impairing of anchorage-independent growth of HaCat cells induced by arsenite.
conclusionOur results demonstrate that PI-3K/Akt-mediated cyclin D1 expression is at least one key event implicated in the arsenite human skin carcinogenic effect.
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