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Udensi UK, Cohly HH, Graham-Evans BE, et al. Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide. Biomark Insights. 2011;6:7-16doi: 10.4137/BMI.S6383.
Udensi, U. K., Cohly, H. H., Graham-Evans, B. E., Ndebele, K., Garcia-Reyero, N., Nanduri, B., Tchounwou, P. B., & Isokpehi, R. D. (2011). Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide. Biomarker insights, 67-16. https://doi.org/10.4137/BMI.S6383
Udensi, Udensi K, et al. "Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide." Biomarker insights vol. 6 (2011): 7-16. doi: https://doi.org/10.4137/BMI.S6383
Udensi UK, Cohly HH, Graham-Evans BE, Ndebele K, Garcia-Reyero N, Nanduri B, Tchounwou PB, Isokpehi RD. Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide. Biomark Insights. 2011 Feb 08;6:7-16. doi: 10.4137/BMI.S6383. PMID: 21461292; PMCID: PMC3065373.
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Biomark Insights. 2011 Feb 08;6:7-16. doi: 10.4137/BMI.S6383.

Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide.

Biomarker insights

Udensi K Udensi, Hari H P Cohly, Barbara E Graham-Evans, Kenneth Ndebele, Natàlia Garcia-Reyero, Bindu Nanduri, Paul B Tchounwou, Raphael D Isokpehi

Affiliations

  1. RCMI-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, Jackson MS 39217, USA.

PMID: 21461292 PMCID: PMC3065373 DOI: 10.4137/BMI.S6383

Abstract

Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes.

Keywords: HaCaT cell; anti-apoptosis; anti-differentiation; arsenic trioxide; chronic exposure; keratinocytes

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