title: Correlation of NM23-H1 cytoplasmic expression with metastatic stage in human prostate cancer tissue.
abstract: Nm23-H1 has been identified as a metastatic suppressor gene in murine melanoma cell lines. Several functions have been attributed to its activity in cancer, including a histidine kinase activity, DNA repair, and regulation of other proteins involved in metastatic formation. While in breast cancer, NM23-H1 overexpression indicates a benign status through impairing progression of disease, its function is opposite in other cancers; e.g., neuroblastoma. To further understand this dichotomy of function in cancer, we have analyzed its function in prostate cancer, in which the relationship between NM23-H1 expression and prognostic state is today controversial. In vitro, overexpression of NM23-H1 in PC3 cells inhibited their cell motility, while downregulation of NM23-H1 expression in these cells by RNA interference showed enhanced cell motility. Immunohistochemistry analysis performed on 346 prostate cancer tissue samples showed a relationship between high levels of NM23-H1 expression in the nuclei of these tumorigenic cells and elevated Gleason score, with high levels of NM23-H1 cytoplasmic staining related to metastatic stage. This retrospective survival study demonstrates that high levels of NM23-H1 expression in the cytoplasm determine recurrence of prostate-specific antigen levels only in those patients with metastatic disease. Our findings suggest a correlation between high levels of NM23-H1 protein in the cytoplasm of the cells and progression of prostate cancer to metastasis, thus definitively identifying NM23-H1 as a new negative prognostic marker in prostate cancer.
authors.affiliation: CEINGE, Via Gaetano Salvatore, 486, 80145, Naples, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Andolfo
authors.forename: Daniela
authors.initials: D
authors.lastname: De Martino
authors.forename: Lucia
authors.initials: L
authors.lastname: Liguori
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Petrosino
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Tata
authors.forename: Alessia
authors.initials: A
authors.lastname: Galasso
authors.forename: Cristin
authors.initials: C
authors.lastname: Roma
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiancone
authors.forename: Stefano
authors.initials: S
authors.lastname: Zarrilli
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Arrigoni
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
authors.forename: Ciro
authors.initials: C
authors.lastname: Imbimbo
authors.forename: Massimo
authors.initials: M
authors.lastname: Zollo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; C517938:NME1 protein, human