2007 Fiscal Year Final Research Report Summary
Investigation into the mechanism of tumorigenesis using p53-deficient epithelial cells
| Project/Area Number |
18592016
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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 |
Morphological basic dentistry
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| Research Institution | Tsurumi University |
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Principal Investigator |
YAMADA Hiroyuki Tsurumi University, School of Dental Medicine, Instructor (90267542)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Ichiro Tsurumi university, School of Dental Medicine, Professor (60147634)
MISHIMA Kenji Tsurumi university, School of Dental Medicine, Assistant Professor (50275343)
INOUE Hiroko Tsurumi university, School of Dental Medicine, Lecturer (50367306)
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| Project Period (FY) |
2006 – 2007
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| Keywords | stromal-epithelial interaction / p53-deficient epithelial cells / tumorigenesis |
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| Research Abstract |
Objective: To dissect the fundamental pathway governing neoplastic conversion of p53-deficient epithelial cells, we established an immortalized duct/ basal cell line (MSE) from the submandibular glands of p53-deficient mice. One of the most provocative implications is that MSE became dramatically tumorigenic (MSA), when co-transplanted with both NIH3T3 (3T3) cells and Matrigel.
Methods: Ten pieces of minced submandibular glands dissected from p53 null mice were placed on cell culture plates coated with type I collagen. After outgrowth, limiting dilution cloning was performed for sorting MSE. Similarly, MSA were also subcloned from tumors derived from xenografts of MSE, Matrigel and 3T3. A variety of culture assays and xenograft experiments were conducted. Results: As compared with MSE, MSA showed cellular pleomorphism and several multinucleated epithelial cells were visible in the monolayer culture. The proliferation rate of MSA was 2-fold higher than MSE. The average number of colonies was higher in MSA than that in MSE, showing significant difference in growth behaviors. In contrast to a highly invasive AdCC, both cell lines, however, lacked invasive capacity. Inoculation of a mixture of MSE and Matrigel reconstructed polarized ducts whereas co-transplantation of MSE with both Matrigel and 3T3 cells developed mixed tumors of adenoma and sarcoma. Overall, MSA gained some transformed phenotypes in vitro, but apparently lacked malignant properties in vivo.
Conclusion : Sarcomatous transformation of 3T3 is a key event in MSE tumorigenesis. The intrinsic tumorigenic programs of p53 null salivary epithelium are promoted by the stromal-epithelial interactions via sarcomatous transformation of 3T3.
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