title: An extensive tumor array analysis supports tumor suppressive role for nucleophosmin in breast cancer.
abstract: Nucleophosmin (NPM) is a multifunctional protein involved in a complex network of interactions. The role of NPM in oncogenesis is controversial. The NPM gene (NPM1) is mutated or rearranged in a number of hematological disorders, but such changes have not been detected in solid cancers. However, experiments with cultured NPM-null cells and with mice carrying a single inactivated NPM allele indicate a tumor suppressor function for NPM. To resolve the role of NPM in solid cancers, we examined its expression and localization in histologically normal breast tissue and a large array of human breast carcinoma samples (n = 1160), and also evaluated its association with clinicopathological variables and patient survival. The intensity and localization (nucleolar, nuclear, cytoplasmic) of NPM varied across clinical samples. No mutations explaining the differences were found, but the present findings indicate that expression levels of NPM affected its localization. Our study also revealed a novel granular staining pattern for NPM, which was an independent prognostic factor of poor prognosis. In addition, reduced levels of NPM protein were associated with poor prognosis. Furthermore, luminal epithelial cells of histologically normal breast displayed high levels of NPM and overexpression of NPM in the invasive MDA-MB-231 cells abrogated their growth in soft agar. These results support a tumor suppressive role for NPM in breast cancer.
authors.affiliation: Research Programs Unit, Molecular Cancer Biology, and Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
authors.forename: Piia-Riitta
authors.initials: PR
authors.lastname: Karhemo
authors.forename: Antti
authors.initials: A
authors.lastname: Rivinoja
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
authors.forename: Maija
authors.initials: M
authors.lastname: Hyvönen
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Chernenko
authors.forename: Johanna
authors.initials: J
authors.lastname: Lammi
authors.forename: Harri
authors.initials: H
authors.lastname: Sihto
authors.forename: Mikael
authors.initials: M
authors.lastname: Lundin
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.forename: Pirjo
authors.initials: P
authors.lastname: Laakkonen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000502:physiology*; D000090243:Nucleophosmin; D013997:Time Factors
chemical_list: D004967:Estrogens; C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D004958:Estradiol