title: Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Golden
authors.forename: Ileana V
authors.initials: IV
authors.lastname: Aragon
authors.forename: Beth
authors.initials: B
authors.lastname: Rutland
authors.forename: J Allan
authors.initials: JA
authors.lastname: Tucker
authors.forename: Lalita A
authors.initials: LA
authors.lastname: Shevde
authors.forename: Rajeev S
authors.initials: RS
authors.lastname: Samant
authors.forename: Guofei
authors.initials: G
authors.lastname: Zhou
authors.forename: Lauren
authors.initials: L
authors.lastname: Amable
authors.forename: Danalea
authors.initials: D
authors.lastname: Skarra
authors.forename: Richard E
authors.initials: RE
authors.lastname: Honkanen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology*; D016923:Cell Death; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins; D018384:Oxidative Stress; D010749:Phosphoprotein Phosphatases; D013912:Threonine; D013997:Time Factors; D014466:Ultraviolet Rays; D015854:Up-Regulation; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D009687:Nuclear Proteins; D013912:Threonine; D014747:Vinblastine; D004317:Doxorubicin; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5