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| Reactive oxygen-induced carcinogenesis causes hypermethylation of p16(Ink4a) and activation of MAP kinase |
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| Author(s): Govindarajan B, Klafter R, Miller MS, Mansur C, Mizesko M, Bai XH, LaMontagne K, Arbiser JL |
| Source: MOLECULAR MEDICINE Volume: 8 Issue: 1 Pages: 1-8 Published: JAN 2002 |
| Times Cited: 43 References: 47 |
| 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.
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| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, 1639 Pierce Dr,WMB 5309, Atlanta, GA 30322 USA |
Addresses:
1. Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA
2. Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Ctr Comprehens Canc, Winston Salem, NC USA
3. Tufts Univ, Sch Med, Dept Dermatol, Medford, MA 02155 USA
4. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg Res, Boston, MA USA |
| Publisher: JOHNS HOPKINS UNIV PRESS, JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: 546UN |
| ISSN: 1076-1551 |
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