DOC-2/hDab2, a candidate tumor suppressor gene involved in the development of gestational trophoblastic diseases.
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.
Fulop
V
V
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Colitti
C V
CV
Genest
D
D
Berkowitz
R S
RS
Yiu
G K
GK
Ng
S W
SW
Szepesi
J
J
Mok
S C
SC
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004396:Coloring Agents; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002820:Hydatidiform Mole, Invasive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D014328:Trophoblastic Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D004396:Coloring Agents; C102885:DAB2 protein, human; D011506:Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D025521:Tumor Suppressor Proteins; C022616:thiazolyl blue