Nickel-induced down-regulation of {Delta}Np63 and its role in the proliferation of keratinocytes

Journal Article · Wed Jun 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.03.024· OSTI ID:21587764

Wenqi, Li ^[1]; Senping, Cheng ^[2]; Hua, Yao ^[3]; Fan, Zhang; Qingshan, Chang ^[2]; Zunji, Ke ^[4]; Xin, Wang; Son, Young-Ok ^[2]; Jia, Luo ^[4]; Xianglin, Shi ^[2]

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1. Department of Preventive Medicine and Environmental Health, University of Kentucky, 121 Washington Avenue, Lexington, KY 40536 (United States)
2. Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)
3. Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003 (China)
4. Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States)

Epidemiological, animal, and cell studies have demonstrated that nickel compounds are human carcinogens. The mechanisms of their carcinogenic actions remain to be investigated. p63, a close homologue of the p53 tumor suppressor protein, has been linked to cell fate determination and/or maintenance of self-renewing populations in several epithelial tissues, including skin, mammary gland, and prostate. {Delta}Np63, a dominant negative isoform of p63, is amplified in a variety of epithelial tumors including squamous cell carcinomas and carcinomas of the prostate and mammary glands. The present study shows that nickel suppressed {Delta}Np63 expression in a short-time treatment (up to 48 h). Nickel treatment caused activation of NF-{kappa}B. Blockage of NF-{kappa}B partially reversed nickel-induced {Delta}Np63 suppression. Nickel decreased interferon regulatory factor (IRF) 3 and IRF7, IKK{epsilon}, and Sp100. Over-expression of IRF3 increased {Delta}Np63 expression suppressed by nickel. Nickel was able to activate p21, and its activation was offset by the over-expression of {Delta}Np63. In turn, elevated p63 expression counteracted the ability of nickel to restrict cell growth. The present study demonstrated that nickel decreased interferon regulatory proteins IRF3 and IRF7, and activated NF-{kappa}B, resulting in {Delta}Np63 suppression and then p21 up-regulation. {Delta}Np63 plays an important role in nickel-induced cell proliferation. - Highlights: > Ni suppressed {Delta}Np63 expression in HaCat cells. > Ni activated NF-{kappa}B, decreased expressions of IRF3 and IRF7, IKK{epsilon}, and Sp100. > Over-expression of IRF3 increased {Delta}Np63 expression suppressed by Ni. > Ni activated p21, and its activation was offset by over-expression of {Delta}Np63. > Elevated p63 expression counteracted the ability of nickel to restrict cell growth.

• OSTI ID: 21587764
• Journal Information: Toxicology and Applied Pharmacology, Vol. 253, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.03.024; PII: S0041-008X(11)00118-9; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENS
CARCINOMAS
CELL PROLIFERATION
INTERFERON
MAMMARY GLANDS
NICKEL
NICKEL CHLORIDES
PROSTATE
BODY
CHLORIDES
CHLORINE COMPOUNDS
DISEASES
ELEMENTS
GLANDS
GROWTH FACTORS
HALIDES
HALOGEN COMPOUNDS
LYMPHOKINES
MALE GENITALS
METALS
MITOGENS
NEOPLASMS
NICKEL COMPOUNDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
TRANSITION ELEMENT COMPOUNDS
TRANSITION ELEMENTS