title: PDCD2 functions in cancer cell proliferation and predicts relapsed leukemia.
abstract: PDCD2 is an evolutionarily conserved eukaryotic protein with unknown function. The Drosophlia PDCD2 ortholog Zfrp8 has an essential function in fly hematopoiesis. Zfrp8 mutants exhibit marked lymph gland hyperplasia that results from increased proliferation of partially differentiated hemocytes, suggesting Zfrp8 may participate in cell growth. Based on the above observations we have focused on the role of PDCD2 in human cancer cell proliferation and hypothesized that aberrant PDCD2 expression may be characteristic of human malignancies. We report that PDCD2 is highly expressed in human acute leukemia cells as well as in normal hematopoietic progenitors. PDCD2 knockdown in cancer cells impairs their proliferation, but not viability relative to parental cells, supporting the notion that PDCD2 overexpression facilitates cancer cell growth. Prospective analysis of PDCD2 in acute leukemia patients indicates PDCD2 RNA expression correlates with disease status and is a significant predictor of clinical relapse. PDCD2's role in cell proliferation and its high expression in human malignancies make it an attractive, novel potential molecular target for new anti-cancer therapies.
authors.affiliation: University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Barboza
authors.forename: Svetlana
authors.initials: S
authors.lastname: Minakhina
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Medina
authors.forename: Binaifer
authors.initials: B
authors.lastname: Balsara
authors.forename: Sonya
authors.initials: S
authors.lastname: Greenwood
authors.forename: Lien
authors.initials: L
authors.lastname: Huzzy
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
authors.forename: Ruth
authors.initials: R
authors.lastname: Steward
authors.forename: Dale G
authors.initials: DG
authors.lastname: Schaar
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C094601:PDCD2 protein, human; D012333:RNA, Messenger
keywords: PDCD2; acute lymphoblastic leukemia; acute myelogenous leukemia; cellular proliferation; hematopoietic stem cells