» Articles » PMID: 11984000

Reactive Oxygen-induced Carcinogenesis Causes Hypermethylation of P16(Ink4a) and Activation of MAP Kinase

Overview
Journal Mol Med
Publisher Biomed Central
Date 2002 May 2
PMID 11984000
Citations 49
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Implantation of foreign materials into mice and humans has been noted to result in the appearance of soft tissue sarcomas at the site of implantation. These materials include metal replacement joints and Dacron vascular grafts. In addition, occupational exposure to nickel has been shown to result in an increased risk of carcinogenesis. The molecular mechanisms of foreign body-induced carcinogenesis are not fully understood.

Materials And Methods: In order to gain insight into these mechanisms, we implanted nickel sulfide into wild type C57BL/6 mice as well as a mouse heterozygous for the tumor suppressor gene, p53. Malignant fibrous histiocytomas arose in all mice, and we have characterized the profile of tumor suppressor genes and signal transduction pathways altered in these cells.

Results: All tumors demonstrated hypermethylation of the tumor suppressor gene p16, as well as activation of the mitogen activated protein kinase (MAP kinase) signaling pathway. This knowledge may be beneficial in the prevention and treatment of tumors caused by foreign body implantation.

Conclusions: Oxidative stress induced by nickel sulfide appears to cause loss of p16 and activation of MAP kinase signaling. These findings support the hypothesis of synergistic interactions between MAP kinase activation and p16 loss in carcinogenesis.

Citing Articles

An Outlook on Platinum-Based Active Ingredients for Dermatologic and Skincare Applications.

Li S, Liu Y, Wu Y, Ren L, Lu Y, Yamaguchi S Nanomaterials (Basel). 2024; 14(15).

PMID: 39120408 PMC: 11314049. DOI: 10.3390/nano14151303.


Epigenetic mechanisms in metal carcinogenesis.

Manic L, Wallace D, Onganer P, Taalab Y, Farooqi A, Antonijevic B Toxicol Rep. 2022; 9:778-787.

PMID: 36561948 PMC: 9764177. DOI: 10.1016/j.toxrep.2022.03.037.


Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis.

Zhao L, Islam R, Wang Y, Zhang X, Liu L Cancers (Basel). 2022; 14(23).

PMID: 36497250 PMC: 9737485. DOI: 10.3390/cancers14235768.


DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype.

Sanna A, Phung B, Mitra S, Lauss M, Choi J, Zhang T JCI Insight. 2022; 7(19).

PMID: 36040798 PMC: 9675437. DOI: 10.1172/jci.insight.156577.


Epithelial-mesenchymal transition: Insights into nickel-induced lung diseases.

Lee H, Jose C, Cuddapah S Semin Cancer Biol. 2021; 76:99-109.

PMID: 34058338 PMC: 8627926. DOI: 10.1016/j.semcancer.2021.05.020.