REGULATION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR EXPRESSION IN SQUAMOUS-CELL CARCINOMA OF THE ORAL CAVITY

被引:52
|
作者
CLAYMAN, G
WANG, SW
NICOLSON, GL
ELNAGGAR, A
MAZAR, A
HENKIN, J
BLASI, F
GOEPFERT, H
BOYD, DD
机构
[1] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEAD & NECK SURG,1515 HOLCOMBE BLVD,HOUSTON,TX 77030
[2] ABBOTT LABS,THROMBOLYT VENTURE GRP,CHICAGO,IL
[3] UNIV MILAN,DEPT GENET MICROBIOL,I-20122 MILAN,ITALY
[4] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030
[5] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,HOUSTON,TX 77030
关键词
D O I
10.1002/ijc.2910540113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We undertook a study to determine the role and regulation of expression of urokinase-type plasminogen activator in squamous-cell carcinoma of the oral cavity. The contribution of urokinase to the invasive process was clearly demonstrated in experiments in which in vitro invasion by a cultured squamous-cell carcinoma cell line was substantially reduced by a monoclonal antibody directed at the catalytic site of urokinase. The conditioned medium from 2 invasive cell lines contained high levels of urokinase. Examination of resected tumors for urokinase revealed (a) localization of the antigen to the tumor cells and (b) higher levels of the plasminogen activator in tumor tissue than in adjacent non-malignant tissue. These results suggested that elevated expression of urokinase is a common feature of this malignancy. The mRNA half-lives of cell lines expressing high and low levels of urokinase were similar, indicating that elevated levels of mRNA for the plasminogen activator were not a consequence of a more stable transcript. No evidence of u-PA gene amplification was obtained by Southern blotting of DNA derived from the cell lines expressing high urokinase levels. Transfection of squamous-cell carcinoma cells, which express high levels of urokinase, with a construct bearing the chloramphenicol acetyl transferase gene driven by the full-length (2345 bp) urokinase promoter indicated activation of the urokinase promoter in trans. In conclusion, our results suggest that transcriptional activation of the urokinase gene, in squamous-cell carcinomas of the oral cavity, leads to elevated levels of urokinase mRNA/protein which, in turn, can promote the invasive phenotype.
引用
收藏
页码:73 / 80
页数:8
相关论文
共 50 条
  • [41] NMR-STUDIES ON UROKINASE-TYPE PLASMINOGEN-ACTIVATOR
    NOWAK, UK
    SMITH, RAG
    DOBSON, CM
    JOURNAL OF CELLULAR BIOCHEMISTRY, 1994, : 159 - 159
  • [42] UROKINASE-TYPE PLASMINOGEN-ACTIVATOR - PROENZYME, RECEPTOR, AND INHIBITORS
    BLASI, F
    VASSALLI, JD
    DANO, K
    JOURNAL OF CELL BIOLOGY, 1987, 104 (04): : 801 - 804
  • [43] PROENZYME TO UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN THE MOUSE INVIVO
    KIELBERG, V
    ANDREASEN, PA
    GRONDAHLHANSEN, J
    NIELSEN, LS
    SKRIVER, L
    DANO, K
    FEBS LETTERS, 1985, 182 (02) : 441 - 445
  • [44] UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN HUMAN ECCRINE SWEAT
    TAKEMURA, T
    HIBINO, T
    SATO, K
    BRITISH JOURNAL OF DERMATOLOGY, 1993, 128 (02) : 178 - 183
  • [45] THE MURINE UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR GENE
    SUH, TT
    NERLOV, C
    DANO, K
    DEGEN, JL
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1994, 269 (42) : 25992 - 25998
  • [46] PLASMINOGEN-ACTIVATOR IN HUMAN ECCRINE SWEAT IS A UROKINASE-TYPE
    TAKEMURA, T
    HIBINO, T
    SATO, K
    CLINICAL RESEARCH, 1988, 36 (03): : A698 - A698
  • [47] PLASMA UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN PATIENTS WITH LEUKEMIAS
    WADA, K
    TAKAHASHI, H
    HANANO, M
    TATEWAKI, W
    NIWANO, H
    SEKI, Y
    SHIBATA, A
    LEUKEMIA & LYMPHOMA, 1994, 15 (5-6) : 499 - 502
  • [48] CONSTRUCTION AND EXPRESSION OF HYBRID PLASMINOGEN ACTIVATORS PREPARED FROM TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR GENES
    LEE, SG
    KALYAN, N
    WILHELM, J
    HUM, WT
    RAPPAPORT, R
    CHENG, SM
    DHEER, S
    URBANO, C
    HARTZELL, RW
    RONCHETTIBLUME, M
    LEVNER, M
    HUNG, PP
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1988, 263 (06) : 2917 - 2924
  • [49] BOVINE EMBRYOS PRODUCE A UROKINASE-TYPE PLASMINOGEN-ACTIVATOR
    BERG, DA
    MENINO, AR
    MOLECULAR REPRODUCTION AND DEVELOPMENT, 1992, 31 (01) : 14 - 19
  • [50] Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity: association with mode of invasion and lymph node metastasis
    Nozaki, S
    Endo, Y
    Kawashiri, S
    Nakagawa, K
    Yamamoto, E
    Yonemura, Y
    Sasaki, T
    ORAL ONCOLOGY, 1998, 34 (01) : 58 - 62