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
Data(s) |
2005
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Resumo |
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. |
Identificador | |
Publicador |
Spandidos Publications |
Relação |
http://www.spandidos-publications.com/ijo/27/3/759 DOI:10.3892/ijo.27.3.759 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. |
Fonte |
School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #Carcinogenesis #Nucleotide excision repair #SPARC/osteonectin/BM-40 #Tumor progression |
Tipo |
Journal Article |