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 [J].
Albertsen, HM ;
Smith, SA ;
Melis, R ;
Williams, B ;
Holik, P ;
Stevens, J ;
White, R .
GENOMICS, 1996, 33 (02) :207-213
[2]   A PHOSPHOTYROSINE INTERACTION DOMAIN [J].
BORK, P ;
MARGOLIS, B .
CELL, 1995, 80 (05) :693-694
[3]   HUMAN SOS1 - A GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR RAS THAT BINDS TO GRB2 [J].
CHARDIN, P ;
CAMONIS, JH ;
GALE, NW ;
VANAELST, L ;
SCHLESSINGER, J ;
WIGLER, MH ;
BARSAGI, D .
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 [J].
CHEUNG, ANY ;
SRIVASTAVA, G ;
PITTALUGA, S ;
MAN, TK ;
NGAN, H ;
COLLINS, RJ .
JOURNAL OF CLINICAL PATHOLOGY, 1993, 46 (03) :204-207
[5]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
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 [J].
FENG, SB ;
CHEN, JK ;
YU, HT ;
SIMON, JA ;
SCHREIBER, SL .
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 [J].
KAVANAUGH, WM ;
TURCK, CW ;
WILLIAMS, LT .
SCIENCE, 1995, 268 (5214) :1177-1179
[10]   AN ALTERNATIVE TO SH2 DOMAINS FOR BINDING TYROSINE-PHOSPHORYLATED PROTEINS [J].
KAVANAUGH, WM ;
WILLIAMS, LT .
SCIENCE, 1994, 266 (5192) :1862-1865