2007 Fiscal Year Final Research Report Summary
Function of REIC/Dkk-3, a putative Wntregulator in normal skin and cancer
| Project/Area Number |
18591249
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Okayama University |
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Principal Investigator |
KATAOKA Ken Okayama University, Department of cell Biology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Assistant Professor (10293317)
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| Co-Investigator(Kenkyū-buntansha) |
SAKOGUCHI Masakiyo Okayama University, Department of cell Biology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Assistant Professor (70379840)
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| Project Period (FY) |
2006 – 2007
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| Keywords | REIC / Dkk-3 / Wnt / Tumor suppressor gene / Skin |
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| Research Abstract |
1. The screening of genes which expression level were elevated after the infection of an adenovirus canying REIC/Dkk-3 (Ad-REIC) into normal human keratinocytes showed that a specific cytokine was strongly induced. After in vitro and in vivo experiments, we conclude that Ad-REIC treatment activates immune reaction against cancer cells through the cytokine in vivo.
2. When over expressed using Ad-REIC, REIC/Dkk-3 induced apoptosisin cancer cells but not in normal cells. Ad-REIC was effective on human prostate cancer (PC3), testicular cancer (NCCIT) and mouse renal carcinoma (RENCA), but not all cancers are sensitive to Ad-REIC. To know the crucial mechanism of Ad-REIC sensitivity, we compared Ad-REIC sensitive renal cancer cells (RENCA) with normal fibroblast (N1H3T3). We found that the expression level of Hsp70/72 affected on tumor-cell specific induction of apoptosis by Ad-REIC.
3. We established Ad-REIC-resistant sub-lines from a prostate cancer cell line (PC3). A micro array analysis to overview the expression profile of these lines is on the way. After the comparison of ER stress response after Ad-REIC treatment, we found a key molecule to be responsible for the Ad-REIC sensitivity.
4. We also established a method for the purification of REIC/Dkk-3 protein from human fibroblasts. We are comparing addition of this type of purified protein with forced expression system by Ad-REIC.
5. Generation of REIC/Dkk-3 knockout mouse is under way. We already got knockout ES cells and we are waiting chimera littermates.
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