Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1905714 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2008 | 12 Pages |
Abstract
Ser/Thr protein phosphatase 5 (PP5) regulates several signaling-cascades that suppress growth and/or facilitate apoptosis in response to genomic stress. The expression of PP5 is responsive to hypoxia inducible factor-1 (HIF-1) and estrogen, which have both been linked to the progression of human breast cancer. Still, it is not clear if PP5 plays a role in the development of human cancer. Here, immunostaining of breast cancer tissue-microarrays (TMAs) revealed a positive correlation between PP5 over-expression and ductal carcinoma in situ (DCIS; P value 0.0028), invasive ductal carcinoma (IDC; P value 0.012) and IDC with metastases at the time of diagnosis (P value 0.0001). In a mouse xenograft model, the constitutive over-expression of PP5 was associated with an increase in the rate of tumor growth. In a MCF-7 cell culture model over-expression correlated with both an increase in the rate of proliferation and protection from cell death induced by oxidative stress, UVC-irradiation, adriamycin, and vinblastine. PP5 over-expression had no apparent effect on the sensitivity of MCF-7 cells to taxol or rapamycin. Western analysis of extracts from cells over-expressing PP5 revealed a decrease in the phosphorylation of known substrates for PP5. Together, these studies indicate that elevated levels of PP5 protein occur in human breast cancer and suggest that PP5 over-expression may aid tumor progression.
Keywords
PP5DNA-PKcsFACSMKK4JnkIDCATRUVCHIF-1DCISASK1c-Jun N-terminal kinaseAdriamycinOxidative stressATMCancerMCF-7 cellsapoptosis signal regulating kinase 1hypoxia inducible factor 1Phosphatasefluorescence activated cell sortingVinblastineDuctal carcinoma in situInvasive ductal carcinomaEstrogen receptorProgesterone receptorglucocorticoid receptor
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Authors
Teresa Golden, Ileana V. Aragon, Beth Rutland, J. Allan Tucker, Lalita A. Shevde, Rajeev S. Samant, Guofei Zhou, Lauren Amable, Danalea Skarra, Richard E. Honkanen,