Related Experiment Videos
Cap43, a novel gene specifically induced by Ni2+ compounds
1The Nelson Institute of Environmental Medicine and The Kaplan Cancer Center, New York University Medical Center, NY 10016, USA.
Cancer Research
|May 30, 1998
Summary
Nickel compounds specifically induce the Cap43 gene, a key factor in nickel toxicity and carcinogenicity. This induction is mediated by increased intracellular calcium levels, suggesting a role in cancer pathogenesis.
Area of Science:
- Molecular toxicology
- Carcinogenesis research
- Gene expression regulation
Background:
- Nickel compounds are known for their essentiality, toxicity, and carcinogenicity.
- Understanding the molecular mechanisms underlying nickel's effects is crucial.
- Identifying specific genes induced by nickel carcinogens can elucidate these mechanisms.
Purpose of the Study:
- To identify genes specifically induced by nickel carcinogens.
- To investigate the molecular signaling pathways involved in nickel-induced gene expression.
- To explore the role of the identified gene in nickel toxicity and cancer.
Main Methods:
- Utilized mRNA differential display technique to identify differentially expressed genes in human lung A549 cells exposed to nickel subsulfide.
- Investigated the induction of the Cap43 gene by various metal compounds, oxidative stress, heat shock, and signaling pathway activators/inhibitors.
- Assessed the role of intracellular calcium (Ca2+) in Cap43 induction using calcium ionophores and chelators.
- Examined Cap43 gene conservation and regulation across species and in different rat organs.
Main Results:
- The Cap43 gene was specifically and significantly induced by nickel compounds (Ni3S2, NiCl2) in A549 cells, with up to a 30-fold increase.
- Other metal compounds, oxidative stress, and heat shock did not induce Cap43, indicating nickel-specificity.
- Cap43 induction was primarily triggered by an elevation of free intracellular Ca2+ caused by Ni2+ exposure.
- The Cap43 gene is evolutionarily conserved and similarly regulated in humans, mice, and rats, and is expressed at lower levels in colon cancer.
Conclusions:
- The Cap43 gene is a nickel-specific target, with its induction mediated by increased intracellular calcium levels.
- Cap43's conserved regulation and altered expression in colon cancer suggest a significant role in cell function and cancer pathogenesis.
- Further research into Cap43 regulation by Ca2+ is warranted to enhance understanding of its role in cancer.