UNIFORM CELL-AUTONOMOUS TUMORIGENESIS OF THE CHOROID-PLEXUS BY PAPOVAVIRUS LARGE T-ANTIGENS

被引:35
作者
CHEN, JD [1 ]
VANDYKE, T [1 ]
机构
[1] UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260
关键词
D O I
10.1128/MCB.11.12.5968
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
The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus is in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis.
引用
收藏
页码:5968 / 5976
页数:9
相关论文
共 65 条
  • [1] HEART AND BONE-TUMORS IN TRANSGENIC MICE
    BEHRINGER, RR
    PESCHON, JJ
    MESSING, A
    GARTSIDE, CL
    HAUSCHKA, SD
    PALMITER, RD
    BRINSTER, RL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (08) : 2648 - 2652
  • [2] MOLECULAR THEMES IN ONCOGENESIS
    BISHOP, JM
    [J]. CELL, 1991, 64 (02) : 235 - 248
  • [3] MALIGNANT-MELANOMA IN TRANSGENIC MICE
    BRADL, M
    KLEINSZANTO, A
    PORTER, S
    MINTZ, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (01) : 164 - 168
  • [4] CHANGES IN THE NUCLEAR-DISTRIBUTION OF CYCLIN (PCNA) BUT NOT ITS SYNTHESIS DEPEND ON DNA-REPLICATION
    BRAVO, R
    MACDONALDBRAVO, H
    [J]. EMBO JOURNAL, 1985, 4 (03) : 655 - 661
  • [5] CYCLIN PCNA IS THE AUXILIARY PROTEIN OF DNA POLYMERASE-DELTA
    BRAVO, R
    FRANK, R
    BLUNDELL, PA
    MACDONALDBRAVO, H
    [J]. NATURE, 1987, 326 (6112) : 515 - 517
  • [6] EXISTENCE OF 2 POPULATIONS OF CYCLIN PROLIFERATING CELL NUCLEAR ANTIGEN DURING THE CELL-CYCLE - ASSOCIATION WITH DNA-REPLICATION SITES
    BRAVO, R
    MACDONALDBRAVO, H
    [J]. JOURNAL OF CELL BIOLOGY, 1987, 105 (04) : 1549 - 1554
  • [7] TRANSGENIC MICE HARBORING SV40 T-ANTIGEN GENES DEVELOP CHARACTERISTIC BRAIN-TUMORS
    BRINSTER, RL
    CHEN, HY
    MESSING, A
    VANDYKE, T
    LEVINE, AJ
    PALMITER, RD
    [J]. CELL, 1984, 37 (02) : 367 - 379
  • [8] ONCOGENES AND SIGNAL TRANSDUCTION
    CANTLEY, LC
    AUGER, KR
    CARPENTER, C
    DUCKWORTH, B
    GRAZIANI, A
    KAPELLER, R
    SOLTOFF, S
    [J]. CELL, 1991, 64 (02) : 281 - 302
  • [9] CECI JD, 1991, ONCOGENE, V6, P323
  • [10] Chen J., UNPUB