アブストラクト(31巻1号:The Bulletin of Kanagawa Dental College)

The Bulletin of Kanagawa Dental College

English

Title : Genetic Disruption of SPARC decreases in ERCC1 expression and induces Skin Papilloma Formation
Subtitle : Selective Proceedings of 37th General Meeting of Kanagawa Odontological Society, 2002
Authors : Yasumasa Kato1, Shinri Koshika1,2, Ryu-Ichiro Hata1,3
Authors(kana) :
Organization : 1Department of Biochemistry and Molecular Biology Kanagawa Dental College, 2Nutritional Biochemistry Program Kanagawa Dental College, 3Research Center of Advanced Technology for Craniomandibular Function Kanagawa Dental College
Journal : The Bulletin of Kanagawa Dental College
Volume : 31
Number : 1
Page : 71-73
Year/Month : 2003 / 3
Article : Report
Publisher : Kanagawa Odontological Society
Abstract : SPARC/osteonectin is a matricellular protein which frequently expressed in a wide variety of human tumors. We have found that treatment with 7,12-dimethylbenz [a] anthracene (DMBA) followed by 12-O-tetradecanoylphorbol 13-acetate (TPA) induced tumors rapidly and high frequently in the dorsal skin of sparc-homozygous null (sparc-null) mice and that the tumors of these mice exhibited much less malignant phenotype than those of wild type mice. Here, we examined a role of endogenous SPARC protein in the process of papilloma formation. When sparc-null fibroblasts (EF (-/-) cells) from whole embryo were treated with DMBA-TPA, transformed foci were obtained with high frequency in EF (-/-) cells. Clearance of DMBA-DNA adducts of EF (-/-) cells was slower than that of wild type cells. Expression of ERCC1, an endonuclease in nucleotide excision repair, decreased in EF (-/-) cells. Using mouse metastatic B16-BL6 melanoma cells, we found that inhibition of SPARC expression by transfection of sparc antisense-expressing vector also increased DMBA-DNA adduct level and sensitivity for cisplatin and UV accompanied with decrease in ERCC1 expression. These results suggest that high papilloma formation in sparc-null mice is due to decrease in the nucleotide excision repair activity by repression of ERCC1 expression.
Practice : Dentistry
Keywords : SPARC, papilloma, DMBA-DNA adduct, NER