Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine

Kato, Yasumasa, Tsukuda, Mamoru, Nagashima, Yoji, Koshika, Shinri, Sakai, Naoki, Yao, Masahiro, Kubota, Yoshinobu, Aoki, Ichiro, Colledge, William H., Foidart, Jean-Michel, Hata, Ryu-Ichiro, & Thompson, Erik W. (2005) Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine. International Journal of Oncology, 27(3), pp. 759-768.

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Abstract

SPARC (secreted protein acidic and rich in cysteine)/ osteonectin/BM-40 is a matricellular protein implicated in development, cell transformation and tumorigenesis. We have examined the role of SPARC in cell transformation induced chemically with 7,12-dimethylbenz[a]anthracene (DMBA) and 12- tetradecanoylphorbol-13-acetate (TPA) in embryonic fibroblasts and in the skin of mice. Embryonic fibroblasts from SPARCnull mice showed increases in cell proliferation, enhanced sensitivity to DMBA and a higher number of DMBA/TPA-induced transformation foci. The number of DMBA-DNA adducts was 9 times higher in SPARCnull fibroblasts and their stability was lower than wild-type fibroblasts, consistent with a reduction in excision repair cross-complementing 1 the nucleotide excision repair enzyme in these cells. The SPARCnull mice showed an increase in both the speed and number of papillomas forming after topical administration of DMBA/TPA to the skin. These papillomas showed reduced growth and reduced progression to a more malignant phenotype, indicating that the effect of SPARC on tumorigenesis depends upon the transformation stage and/or tissue context. These data reinforce a growing number of observations in which SPARC has shown opposite effects on different tumor types/stages.

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1 citations in Web of Science®
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ID Code: 72575
Item Type: Journal Article
Refereed: Yes
Keywords: Carcinogenesis, Nucleotide excision repair, SPARC/osteonectin/BM-40, Tumor progression
DOI: 10.3892/ijo.27.3.759
ISSN: 1019-6439
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 04 Jun 2014 04:14
Last Modified: 04 Jun 2014 04:25

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