ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Silencing KRAS overexpression in arsenic-transformed prostate epithelial and stem cells partially mitigates malignant phenotype.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Urinary Trace Element Concentrations in Congolese Patients With Prostate Cancer: A Case-Control Study.Prostate cancer · 2026Article
- Prostate Cancer: Emerging Modifiable Risk Factors and Therapeutic Strategies in the Management of Advanced Cancer.Life (Basel, Switzerland) · 2024Review
- Arsenic-induced prostate cancer: an enigma.Medical oncology (Northwood, London, England) · 2024Review
- Stem Cells as Target for Prostate cancer Therapy: Opportunities and Challenges.Stem cell reviews and reports · 2022Review
- Arsenic activates STAT3 signaling during the transformation of the human bronchial epithelial cells.Toxicology and applied pharmacology · 2022Article
- The role of autophagy in metal-induced urogenital carcinogenesis.Seminars in cancer biology · 2021Review
- KRAS-retroviral fusion transcripts and gene amplification in arsenic-transformed, human prostate CAsE-PE cancer cells.Toxicology and applied pharmacology · 2020Article
- Metal carcinogen exposure induces cancer stem cell-like property through epigenetic reprograming: A novel mechanism of metal carcinogenesis.Seminars in cancer biology · 2019Review
- Arsenite malignantly transforms human prostate epithelial cells in vitro by gene amplification of mutated KRAS.PloS one · 2019Article
- Arsenic Alters Exosome Quantity and Cargo to Mediate Stem Cell Recruitment Into a Cancer Stem Cell-Like Phenotype.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer.Journal of experimental & clinical cancer research : CR · 2017Article
- AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR signaling pathway.Oncology letters · 2017Article
- Gli Transcription Factors Mediate the Oncogenic Transformation of Prostate Basal Cells Induced by a Kras-Androgen Receptor Axis.The Journal of biological chemistry · 2016Article
- Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration.Toxicology and applied pharmacology · 2016Article
- Silencing KRAS Overexpression in Cadmium-Transformed Prostate Epithelial Cells Mitigates Malignant Phenotype.Chemical research in toxicology · 2016Article
- Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study.Environmental research · 2016Article
- Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells.Oncotarget · 2016Article
- Oxidative stress, epigenetics, and cancer stem cells in arsenic carcinogenesis and prevention.Current pharmacology reports · 2016Article
- Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis.Toxicology and applied pharmacology · 2015Article
- Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells.Toxicology and applied pharmacology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Inorganic arsenic is a human carcinogen that likely targets the prostate. Chronic arsenic exposure malignantly transforms the RWPE-1 human prostate epithelial line to chronic arsenic exposed-prostate epithelial (CAsE-PE) cells, and a derivative normal prostate stem cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs). The KRAS oncogene is highly overexpressed in CAsE-PE cells and activation precedes transformation, inferring mechanistic significance. As-CSCs also highly overexpress KRAS. Thus, we hypothesize KRAS activation is key in causing and maintaining an arsenic-induced malignant phenotype, and hence, KRAS knockdown (KD) may reverse this malignant phenotype. RNA interference using shRNAmirs to obtain KRAS KD was used in CAsE-PE and As-CSC cells. Cells analyzed 2 weeks post transduction showed KRAS protein decreased to 5% of control after KD, confirming stable KD. KRAS KD decreased phosphorylated ERK, indicating inhibition of RAS/ERK signaling, a proliferation/survival pathway activated with arsenic transformation. Secreted metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but KRAS KD from 4 weeks on decreased secreted MMP-9 activity by 50% in As-CSCs. Colony formation, a characteristic of cancer cells, was decreased in both KRAS KD transformants. KRAS KD also decreased the invasive capacity of both cell types. KRAS KD decreased proliferation in As-CSCs, consistent with loss of rapid tumor growth. Genes predicted to impact cell proliferation (eg, Cyclin D1, p16, and p21) changed accordingly in both KD cell types. Thus, KRAS silencing impacts aspects of arsenic-induced malignant phenotype, inducing loss of many typical cancer characteristics particularly in As-CSCs.
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