DOC-2/hDab2, a candidate tumor suppressor gene involved in the development of gestational trophoblastic diseases

被引:77
作者
Fulop, V
Colitti, CV
Genest, D
Berkowitz, RS
Yiu, GK
Ng, SW
Szepesi, J
Mok, SC [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol,Lab Gynecol Oncol, Boston, MA 02115 USA
[2] Haymal Imre Univ Hlth Sci, Dept Obstet & Gynecol, Budapest, Hungary
关键词
trophoblastic diseases; DOC-2; Dab2; tumor suppressor; cancer;
D O I
10.1038/sj.onc.1201955
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
Gestational trophoblastic diseases comprise a spectrum of interrelated diseases including partial mole, complete mole and gestational choriocarcinoma, Using reverse transcriptase PCR (RT-PCR) analysis, we identified higher levels of DOC-2/hDab2 expression in the normal trophoblast cells in culture than in choriocarcinoma cell lines. Subsequent study using immunohistochemistry showed high levels of DOC-2/hDab2 protein expression in normal trophoblast tissues but significantly lower levels of expression in gestational trophoblastic disease tissues, particularly in complete mole and choriocarcinoma. When DOC-2/hDab2 was transfected into the choriocarcinoma cell lines, Jar, JEG and BeWo, the stable transfectants showed significantly reduced growth rate in culture. These data suggest that down regulation of DOC-2/hDab2 may play an important role in the development of gestational trophoblastic diseases.
引用
收藏
页码:419 / 424
页数:6
相关论文
共 19 条
  • [1] Sequence, genomic structure, and chromosomal assignment of human DOC-2
    Albertsen, HM
    Smith, SA
    Melis, R
    Williams, B
    Holik, P
    Stevens, J
    White, R
    [J]. GENOMICS, 1996, 33 (02) : 207 - 213
  • [2] A PHOSPHOTYROSINE INTERACTION DOMAIN
    BORK, P
    MARGOLIS, B
    [J]. CELL, 1995, 80 (05) : 693 - 694
  • [3] HUMAN SOS1 - A GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR RAS THAT BINDS TO GRB2
    CHARDIN, P
    CAMONIS, JH
    GALE, NW
    VANAELST, L
    SCHLESSINGER, J
    WIGLER, MH
    BARSAGI, D
    [J]. SCIENCE, 1993, 260 (5112) : 1338 - 1343
  • [4] EXPRESSION OF C-MYC AND C-FMS ONCOGENES IN TROPHOBLASTIC CELLS IN HYDATIDIFORM MOLE AND NORMAL HUMAN PLACENTA
    CHEUNG, ANY
    SRIVASTAVA, G
    PITTALUGA, S
    MAN, TK
    NGAN, H
    COLLINS, RJ
    [J]. JOURNAL OF CLINICAL PATHOLOGY, 1993, 46 (03) : 204 - 207
  • [5] ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE
    CHIRGWIN, JM
    PRZYBYLA, AE
    MACDONALD, RJ
    RUTTER, WJ
    [J]. BIOCHEMISTRY, 1979, 18 (24) : 5294 - 5299
  • [6] 2 BINDING ORIENTATIONS FOR PEPTIDES TO THE SRC SH3 DOMAIN - DEVELOPMENT OF A GENERAL-MODEL FOR SH3-LIGAND INTERACTIONS
    FENG, SB
    CHEN, JK
    YU, HT
    SIMON, JA
    SCHREIBER, SL
    [J]. SCIENCE, 1994, 266 (5188) : 1241 - 1247
  • [7] FULOP V, 1998, IN PRESS J REPROD ME
  • [8] Hancock BW, 1997, GESTATIONAL TROPHOBL
  • [9] PTB DOMAIN BINDING TO SIGNALING PROTEINS THROUGH A SEQUENCE MOTIF CONTAINING PHOSPHOTYROSINE
    KAVANAUGH, WM
    TURCK, CW
    WILLIAMS, LT
    [J]. SCIENCE, 1995, 268 (5214) : 1177 - 1179
  • [10] AN ALTERNATIVE TO SH2 DOMAINS FOR BINDING TYROSINE-PHOSPHORYLATED PROTEINS
    KAVANAUGH, WM
    WILLIAMS, LT
    [J]. SCIENCE, 1994, 266 (5192) : 1862 - 1865