2006 Fiscal Year Final Research Report Summary
Construction and analysis of a model mouse with cancer caused by oxidative stress.
| Project/Area Number |
17500291
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory animal science
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
ISHII Naoaki Tokai University, School of Medicine, Professor, 医学部, 教授 (60096196)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | Mitochondria / Electron transport / Complex II / SDHC / Reactive oxygen species / apoptosis / Paraganglioma / transgenic mouse |
|---|
| Research Abstract |
A mutation in a subunit, cytochrome b large subunit (C.elegans : CYT-1 ; mouse and human : SDHC), of complex II in electron transport system, results in increasing O_2^- production and therefore lead to abnormal energy metabolism and apoptosis. Recently, individuals with an inherited propensity for vascularized head and neck tumors (i.e., paragangliomas) have been demonstrated to contain one of several mutations in complex II. To further explore the role of oxidative stress from mitochondria on cancer, we established transgenic cell line and mouse with a point mutation in the SDHC gene.
There were many apoptotic cells in this cell line, and some cells that escaped from apoptosis underwent transformation. Oxidative stress from mitochondria leads to pathology such as apoptosis resulting precocious aging and also transformation resulting tumorigenesis. The supernumerary apoptosis was induced by activation of a signal transduction pathway via mitochondria. The induction of the apoptosis may enhance the reduction of a number of survived cells in aged cells suppressed cell growth ability and, on the other hand, may have an effect of growth suppression in transformed cells having hyper-oxidative stress. It is suggested that oxidative stress is deeply related with benign tumorigenic transformation by tumor suppression via the apoptosis.
To verify the phenomena at a mammalian individual level, we have constructed conditional transgenic mouse with Tet-on/off system with an amino acid mutated SDHC gene. The inductions of the transgenic gene by tetracycline were found in several organs and tissues except brain and muscle. Being hyper-sensitive to oxidative stress, the transgenic mouse is anticipated as a model mouse with cancer caused by oxidative stress.
|
Research Products
(30 results)
