Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Nickel-induced transformation shifts the balance between HIF-1 and p53 transcription factors.

Authors: Salnikow, K; An, W G; Melillo, G; Blagosklonny, M V; Costa, M

Published In Carcinogenesis, (1999 Sep)

Abstract: Nickel (Ni) compounds are potent carcinogens and can induce malignant transformation of rodent and human cells. In an attempt to unravel the molecular mechanisms of Ni-induced transformation we investigated transcriptional activity of hypoxia-inducible factor (HIF-1) and p53 tumor suppressor protein in Ni-transformed cells. We demonstrated that the activity of HIF-1-responsive promoters was increased in Ni-transformed rodent cells resulting in the increased ratio between HIF-1- and p53-stimulated transcription. To further elucidate the roles of HIF-1 and p53 in Ni-induced transformation we used human osteosarcoma (HOS) cells and a Ni-transformed derivative, SA-8 cells. Since non-functional p53 was expressed in both HOS and SA-8 cells, acute Ni treatment induced HIF-1alpha protein and HIF-1-dependent transcription without affecting p53. In MCF-7 and A549, human cancer cells with the wild-type p53, both functional p53 and HIF-1alpha proteins accumulated following exposure to Ni. The induction of HIF-1alpha and wild-type p53 by Ni was detected after 6 h and was most pronounced by 24 h. These results suggest that acute Ni treatment causes accumulation of HIF-1alpha protein and simultaneous accumulation of wild-type, but not mutant, p53. We suggest that the induction of hypoxia-like conditions in Ni-treated cells with subsequent selection for increased HIF-1-dependent transcription is involved in Ni-induced carcinogenesis.

PubMed ID: 10469629 Exiting the NIEHS site

MeSH Terms: 3T3 Cells/drug effects; Adenocarcinoma/pathology; Animals; Bone Neoplasms/pathology; Breast Neoplasms/pathology; Bronchi/cytology; Cadmium Chloride/toxicity; Carcinogens, Environmental/toxicity*; Cell Hypoxia; Cell Transformation, Neoplastic/drug effects*; Cobalt/toxicity; Cricetinae; Cricetulus; DNA-Binding Proteins/metabolism*; Epithelial Cells/drug effects; Fibroblasts/drug effects; Gene Expression Regulation/drug effects*; Genes, p53; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms/pathology; Mice; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Nickel/toxicity*; Nuclear Proteins/metabolism*; Osteosarcoma/pathology; Promoter Regions, Genetic; Recombinant Fusion Proteins/metabolism; Transcription Factors*; Transcription, Genetic/drug effects*; Tumor Cells, Cultured; Tumor Suppressor Protein p53/metabolism*

to Top