A potential role for PTTG/securin in the developing human fetal brain

被引:39
作者
Boelaert, K
Tannahill, LA
Bulmer, JN
Kachilele, S
Chan, SY
Kim, D
Gittoes, NJL
Franklyn, JA
Kilby, MD
Mccabe, CJ
机构
[1] Univ Birmingham, Queen Elizabeth Hosp, Div Med Sci, Birmingham B15 2TH, W Midlands, England
[2] Univ Birmingham, Queen Elizabeth Hosp, Div Reprod & Child Hlth, Birmingham B15 2TH, W Midlands, England
[3] Univ Newcastle Upon Tyne, Royal Victoria Infirm, Dept Pathol, Sch Clin & Lab Sci, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
关键词
embryonic expression; proliferation; NT-2;
D O I
10.1096/fj.02-0948com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human securin, known also as PTTG, has established oncogenic and cell cycle regulatory functions. PTTG/securin transforms cells in vitro, inhibits sister chromatid separation, and regulates secretion of fibroblast growth factor-2. FGF-2 is a key regulator of CNS development and PTTG/securin expression has been reported in murine fetal brain. We examined the expression and function of securin and FGF-2 in the developing human fetal brain and in a fetal neuronal cell line (NT 2). Securin expression was significantly reduced in first and second trimester fetal cerebral cortex compared with adult cerebral cortex, where immunocytochemistry revealed intense securin staining in neuronal cell bodies. FGF-2 protein was concordantly lower in fetal cortex, whereas pretranslational expression of PTTG binding factor (PBF) was not significantly altered in fetal brain compared with adult. PCNA expression demonstrated that high securin levels in adult cortex were associated with absent cell proliferation. In NT-2 cells, securin stimulated FGF-2 expression, which could be abrogated by a carboxyl-terminal mutation. Low transient expression of securin resulted in a significant proliferative effect, whereas high levels of securin expression inhibited cell turnover. We propose a potential role for human PTTG/securin in modulating cell proliferation and FGF-2 expression during human neurogenesis.
引用
收藏
页码:1631 / 1639
页数:9
相关论文
共 44 条
  • [31] *POLK REP, 1998, REV GUID RES US FET
  • [32] FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells
    Qian, XM
    Davis, AA
    Goderie, SK
    Temple, S
    [J]. NEURON, 1997, 18 (01) : 81 - 93
  • [33] Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product
    Ramos-Morales, F
    Domínguez, A
    Romero, F
    Luna, R
    Multon, MC
    Pintor-Toro, JA
    Tortolero, M
    [J]. ONCOGENE, 2000, 19 (03) : 403 - 409
  • [34] PROLIFERATION, DIFFERENTIATION, AND LONG-TERM CULTURE OF PRIMARY HIPPOCAMPAL-NEURONS
    RAY, J
    PETERSON, DA
    SCHINSTINE, M
    GAGE, FH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (08) : 3602 - 3606
  • [35] GENETIC RESEARCH IN EMBRYOLOGY
    SCHMUTZLER, RK
    [J]. HUMAN REPRODUCTION, 1992, 7 : 25 - 29
  • [36] Expression of PTTG and prc1 genes during telencephalic neurogenesis
    Tarabykin, V
    Britanova, O
    Fradkov, A
    Voss, A
    Katz, LS
    Lukyanov, S
    Gruss, P
    [J]. MECHANISMS OF DEVELOPMENT, 2000, 92 (02) : 301 - 304
  • [37] FUNCTIONS OF BASIC FIBROBLAST GROWTH-FACTOR AND NEUROTROPHINS IN THE DIFFERENTIATION OF HIPPOCAMPAL-NEURONS
    VICARIOABEJON, C
    JOHE, KK
    HAZEL, TG
    COLLAZO, D
    MCKAY, RDG
    [J]. NEURON, 1995, 15 (01) : 105 - 114
  • [38] Mice lacking pituitary tumor transforming gene show testicular and splenic hypoplasia, thymic hyperplasia, thrombocytopenia, aberrant cell cycle progression, and premature centromere division
    Wang, ZY
    Yu, R
    Melmed, S
    [J]. MOLECULAR ENDOCRINOLOGY, 2001, 15 (11) : 1870 - 1879
  • [39] LOCALIZATION OF BFGF AND FGF-RECEPTOR IN THE DEVELOPING NERVOUS-SYSTEM OF THE EMBRYONIC AND NEWBORN RAT
    WEISE, B
    JANET, T
    GROTHE, C
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 1993, 34 (04) : 442 - 453
  • [40] Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: Evidence from live cell imaging
    Yu, R
    Ren, SG
    Horwitz, GA
    Wang, ZY
    Melmed, S
    [J]. MOLECULAR ENDOCRINOLOGY, 2000, 14 (08) : 1137 - 1146