Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer.
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.
Golden
Teresa
T
Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL 36688, USA.
Aragon
Ileana V
IV
Rutland
Beth
B
Tucker
J Allan
JA
Shevde
Lalita A
LA
Samant
Rajeev S
RS
Zhou
Guofei
G
Amable
Lauren
L
Skarra
Danalea
D
Honkanen
Richard E
RE
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
D009687:Nuclear Proteins; D013912:Threonine; D014747:Vinblastine; D004317:Doxorubicin; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5