Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer
- 作者：Teresa Golden ; Ileana V. Aragon ; Beth Rutl ; J. Allan Tucker ; Lalita A. Shevde ; Rajeev S. Samant ; Guofei Zhou ; Lauren Amable ; Danalea Skarra ; Richard E. Honkanen
- 关键词：Phosphatase ; PP5 ; UVC ; Adriamycin ; Vinblastine ; Oxidative stress ; MCF-7 cells ; Cancer
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
- 出版年：2008
- 期刊代码：19_09254439
- 类别：bio
- 出版时间：April 2008
- 卷：1782
- 期：4
- 页码：259-270
- 文件大小：1488 K
摘要
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.