Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1782, Issue 4, Pages 259-270Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2008.01.004
Keywords
phosphatase; PP5; UVC; adriamycin; vinblastine; oxidative stress; MCF-7 cells; cancer
Funding
- NCI NIH HHS [R01 CA060750-14S1, R01 CA060750-15, CA-60750, R01 CA060750-14, R01 CA060750] Funding Source: Medline
- NCRR NIH HHS [C06 RR11174] Funding Source: Medline
- NIMHD NIH HHS [P20 MD002314, P20 MD-002314, P20 MD002314-01] Funding Source: Medline
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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. (C) 2008 Elsevier B.V. All rights reserved.
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