title: Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate.
abstract: BACKGROUND
  In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-alpha, IL-1) stimulation.
  
  
  METHODS
  Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades).
  
  
  RESULTS
  In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason).
  
  
  CONCLUSIONS
  IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1alpha and TNFalpha might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1alpha and TNFalpha would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2).
authors.affiliation: Department of Cell Biology and Genetics, University of Alcalá; 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Rodríguez-Berriguete
authors.forename: Benito
authors.initials: B
authors.lastname: Fraile
authors.forename: Fermín R
authors.initials: FR
authors.lastname: de Bethencourt
authors.forename: Angela
authors.initials: A
authors.lastname: Prieto-Folgado
authors.forename: Nahikari
authors.initials: N
authors.lastname: Bartolome
authors.forename: Claudia
authors.initials: C
authors.lastname: Nuñez
authors.forename: Bruna
authors.initials: B
authors.lastname: Prati
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Onsurbe
authors.forename: Gabriel
authors.initials: G
authors.lastname: Olmedilla
authors.forename: Ricardo
authors.initials: R
authors.lastname: Paniagua
authors.forename: Mar
authors.initials: M
authors.lastname: Royuela
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D053582:Interleukin-1alpha / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha