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Biochim Biophys Acta. 2008 Apr;1782(4):259-70. doi: 10.1016/j.bbadis.2008.01.004. Epub 2008 Jan 26.

Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer.

Author information

1
Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL 36688, USA.

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.

PMID:
18280813
PMCID:
PMC2505351
DOI:
10.1016/j.bbadis.2008.01.004
[Indexed for MEDLINE]
Free PMC Article

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