title: Cellular interactions of the phosphorylated form of AKT in prostate cancer.
abstract: Phospho-Akt (P-Akt1) promotes proliferation and increased survival in vitro and plays an important role in prostate cancer (PCa) progression as well as the prediction of the probability of recurrence. In this study, the goal was to demonstrate the involvement and impact of P-Akt1 on cellular interactions, biomechanisms, and pathways in PCa. Tissue microarrays from 640 PCa patients were immunostained with various antibodies. Ki-67 was used to measure proliferation index, and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling was used for apoptotic index. Increased expression of P-Akt1 was associated with an increased proliferation but inversely correlated with apoptotic index. Higher levels of P-Akt1 are associated with both higher levels of cytoplasmic p27 and higher levels of nuclear p27, suggesting an involvement in both cytoplasmic entrapment and phosphorylation of p27. P-Akt1 expression significantly correlated with nuclear and cytoplasmic staining of FHKR and GSK. The strongest correlations were found with the P- forms of both, suggesting enzyme kinetics in the latter. Here, phosphorylation is the principal method of FHKR and GSK inactivation. P-Akt1 correlated with nuclear transcription factor kappa B, suggesting a role in the inhibition through phosphorylation of nuclear transcription factor kappa B. The results of the current study are unique because of the scope of the markers and the size of the population used. In vitro- and in vivo-derived information of P-Akt1 and its downstream effectors demonstrates significant involvement in PCa. Our data suggest that PCa uses multiple mechanisms to regulate this pathway and substantiate the concept of redundancy in cancer pathway regulation. Consequently, new hypothesis-driven studies can be derived from this information.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030. Electronic address: kai.hammerich@nih.gov.
authors.forename: Kai H
authors.initials: KH
authors.lastname: Hammerich
authors.affiliation: The Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Anna
authors.initials: A
authors.lastname: Frolov
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Rile
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030; The Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030; Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston, TX 77030. Electronic address: Gustavo.E.Ayala@uth.tmc.edu.
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D000071161:Forkhead Box Protein O1 / Q000032:analysis; D038341:Glycogen Synthase Kinases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis*; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D016328:NF-kappa B; D050760:Cyclin-Dependent Kinase Inhibitor p27; D038341:Glycogen Synthase Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Cancer pathway regulation; Immunohistochemistry; Prognosis; Prostate cancer–related death; Prostate carcinoma; Tumor marker