title: PCNA levels in neuroblastoma are increased in tumors with an amplified N-myc gene and in metastatic stage tumors.
abstract: N-myc oncogene amplification in neuroblastoma has been found to be significantly associated with advanced stage disease and tumor progression. However, there is a lack of data on tumors, regarding the relationship between N-myc gene amplification and proliferation activity. Proliferating cell nuclear antigen (PCNA) is a proliferation-induced 36 kD nuclear protein that is the auxiliary component of DNA polymerase delta. PCNA levels in tissues have been found to correlate with proliferative activity. We have examined PCNA levels in neuroblastomas in relation to N-myc gene amplification and tumor stage. Statistically, significantly higher levels of PCNA were observed in tumors with an amplified N-myc gene relative to tumors with a single gene copy. The highest levels of PCNA were observed in advanced stage tumors with an amplified N-myc gene. Treatment of neuroblastoma cells in culture with retinoic acid, which induces differentiation, resulted in a substantial decrease in PCNA. Our results suggest that PCNA levels may reflect differences in proliferative activity between neuroblastomas, related to stage of the disease and to N-myc gene copy number.
authors.affiliation: University of Michigan Medical School, Department of Pediatric Hematology, Ann Arbor 48109-0510.
authors.forename: D R
authors.initials: DR
authors.lastname: Keim
authors.forename: N
authors.initials: N
authors.lastname: Hailat
authors.forename: R
authors.initials: R
authors.lastname: Kuick
authors.forename: C P
authors.initials: CP
authors.lastname: Reynolds
authors.forename: G M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: R C
authors.initials: RC
authors.lastname: Seeger
authors.forename: S M
authors.initials: SM
authors.lastname: Hanash
mesh_terms: D000595:Amino Acid Sequence; D002455:Cell Division / Q000502:physiology; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D009687:Nuclear Proteins / Q000032:analysis*; D018809:Proliferating Cell Nuclear Antigen; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen