Arsenic-induced malignant transformation of human keratinocytes: involvement of Nrf2.

ABSTRACT: Arsenic is a well-known human skin carcinogen but the underlying mechanisms of carcinogenesis are unclear. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism, and emerging data suggest that constitutive activation of Nrf2 contributes to malignant phenotype. In the present study when an immortalized, nontumorigenic human keratinocyte cell line (HaCaT) was continuously exposed to an environmentally relevant level of inorganic arsenite (100 nM) for 28 weeks, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. To investigate the mechanisms involved, a broad array of biomarkers for transformation were assessed in these arsenic-transformed cells (termed

SUBMITTER: Pi J 

PROVIDER: S-EPMC2658531 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature