Cadmium Induction Pathway

Preferred Label : Cadmium Induction Pathway;

NCIt related terms : Cadmium induces DNA synthesis and proliferation in macrophages;

Alternative definition : BIOCARTA: Exposure to divalent cadmium ions (Cd2 ) is a known cancer risk factor, but the molecular mechanisms responsible for the inappropriate induction of cellular proliferation by cadmium are still being figured out. One cellular model used to study this process is macrophages grown in culture. In cultured macrophages, cadmium acts both at the cell surface and in the cytoplasm to induce proliferation. At the cell surface, cadmium interacts with a pertussis-sensitive cell surface receptor, probably a Gi-coupled GPCR, to stimulate proliferation. Cadmium can enter cells through calcium ion channels and once in cells affects calcium release by the ER. In addition to changes in intracellular calcium, the proliferative effects of cadmium are mediated by the Ras/Map kinase pathway, and also NF-kB. Inhibition of phospholipase C, map kinases, or NF-kB with a variety of pharmacological inhibitors all blocked the activation of cellular proliferation by cadmium. Protein kinase C is also activated by cadmium, upstream of the Map kinase pathway. Changes in transcription induced by cadmium include induction of immediate early genes like fos, jun, and myc. In addition to inducing cellular proliferation, cadmium also is slightly genotoxic due to inhibition of DNA repair, activates stress genes, and inhibits the immune system. The immunomodulatory effects observed with cadmium treatment may also involvement transcriptional disregulation, including the expression of cytokines such as IL-4, IL-10, and TNF-alpha. Although macrophages have been used for many studies, other cell types are also the target of cadmium's toxicity. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_cdMacPathway;

Details

Origin ID

C39023;

UMLS CUI

C1511475;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 2 [NCIt concept]
- GTPase HRas [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Myc Proto-Oncogene Protein [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Protein Kinase C Alpha Type [NCIt concept]
- Proto-Oncogene c-Fos [NCIt concept]
- RAF Proto-Oncogene Serine/Threonine-Protein Kinase [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
pathway_has_gene_element
- FOS wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAP2K2 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- MYC wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- PRKCA wt Allele [NCIt concept]
- RAF1 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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