PURPOSE: Whereas the early stage of prostate cancer is marked by excessive proliferation, in advanced stages of the disease, a decreased apoptotic death rate (increased cell survival) also contributes to net tumor growth. Altered regulation of the mitogen-activated protein kinase (MAPK)-regulated cell proliferation and Akt-regulated cell survival pathways are suspected causes. In this study, we wanted to determine: (a) whether the degree of Akt activation can be assessed by immunohistochemical staining of paraffin- embedded human prostate cancer biopsies with an antibody to phospho-Akt (Ser473); and (b) whether phospho-MAPK/Erk1/2 and phospho-Akt expression are altered in prostate cancer. EXPERIMENTAL DESIGN: To examine the activation status of MAPK/Erk1/2 and Akt, archival paraffin-embedded sections from 74 cases of resected prostate cancer were immunostained with antibodies to phospho-MAPK/Erk1/2 (Thr202/ Tyr204) and phospho-Akt (Ser473). RESULTS: The staining intensity for phospho-Akt was significantly greater in Gleason grades 8-10 (92% of such cases staining strongly) compared with prostatic intraepithelial neoplasia and all other grades of prostate cancer (only 10% of these cases staining strongly; P < or = 0.001). The staining intensity for phospho-MAPK/Erk, on the other hand, was significantly greater for normal, hyperplastic, and prostatic intraepithelial neoplasia lesions but declined with disease progression, reaching its lowest level of expression in high Gleason grades 8-10 (P < 0.0001). CONCLUSION: The activation state of the cell survival protein Akt can be analyzed in human prostate cancer by immunohistochemical staining of paraffin-embedded tissue with a phospho-specific Akt (Ser473) antibody. Advanced disease is accompanied by activation of Akt and inactivation of Erk.
PURPOSE: Whereas the early stage of prostate cancer is marked by excessive proliferation, in advanced stages of the disease, a decreased apoptotic death rate (increased cell survival) also contributes to net tumor growth. Altered regulation of the mitogen-activated protein kinase (MAPK)-regulated cell proliferation and Akt-regulated cell survival pathways are suspected causes. In this study, we wanted to determine: (a) whether the degree of Akt activation can be assessed by immunohistochemical staining of paraffin- embedded humanprostate cancer biopsies with an antibody to phospho-Akt (Ser473); and (b) whether phospho-MAPK/Erk1/2 and phospho-Akt expression are altered in prostate cancer. EXPERIMENTAL DESIGN: To examine the activation status of MAPK/Erk1/2 and Akt, archival paraffin-embedded sections from 74 cases of resected prostate cancer were immunostained with antibodies to phospho-MAPK/Erk1/2 (Thr202/ Tyr204) and phospho-Akt (Ser473). RESULTS: The staining intensity for phospho-Akt was significantly greater in Gleason grades 8-10 (92% of such cases staining strongly) compared with prostatic intraepithelial neoplasia and all other grades of prostate cancer (only 10% of these cases staining strongly; P < or = 0.001). The staining intensity for phospho-MAPK/Erk, on the other hand, was significantly greater for normal, hyperplastic, and prostatic intraepithelial neoplasia lesions but declined with disease progression, reaching its lowest level of expression in high Gleason grades 8-10 (P < 0.0001). CONCLUSION: The activation state of the cell survival protein Akt can be analyzed in humanprostate cancer by immunohistochemical staining of paraffin-embedded tissue with a phospho-specific Akt (Ser473) antibody. Advanced disease is accompanied by activation of Akt and inactivation of Erk.
Authors: Stephane Terry; Luis Queires; Sixtina Gil-Diez-de-Medina; Min-Wei Chen; Alexandre de la Taille; Yves Allory; Phuong-Lan Tran; Claude C Abbou; Ralph Buttyan; Francis Vacherot Journal: Prostate Date: 2006-07-01 Impact factor: 4.104
Authors: Ferenc G Rick; Andrew V Schally; Luca Szalontay; Norman L Block; Karoly Szepeshazi; Mehrdad Nadji; Marta Zarandi; Florian Hohla; Stefan Buchholz; Stephan Seitz Journal: Proc Natl Acad Sci U S A Date: 2012-01-18 Impact factor: 11.205
Authors: Hui Gao; Xuesong Ouyang; Whitney A Banach-Petrosky; William L Gerald; Michael M Shen; Cory Abate-Shen Journal: Proc Natl Acad Sci U S A Date: 2006-09-14 Impact factor: 11.205
Authors: Addanki P Kumar; Shylesh Bhaskaran; Manonmani Ganapathy; Katherine Crosby; Michael D Davis; Peter Kochunov; John Schoolfield; I-Tien Yeh; Dean A Troyer; Rita Ghosh Journal: Clin Cancer Res Date: 2007-05-01 Impact factor: 12.531