Successive activation of the platelet-derived growth factor beta receptor and platelet-derived growth factor B genes correlates with the genesis of human choriocarcinoma.
The hydatidiform mole is a benign disease of the placenta characterized by the absence of the maternal genome. Approximately 3% of the reported cases will develop into malignant choriocarcinoma. In situ hybridization analysis reveals that the paternal platelet-derived growth factor (PDGF) beta receptor gene is up to 2 orders of magnitude more active in cytotrophoblasts of the complete hydatidiform moles than in normal placentae. The transition between hyperplasia (complete hydatidiform mole) and neoplasia (choriocarcinoma) in these cells correlates with at least a 10- to 20-fold activation of the PDGF-B gene. Since the neoplastic cytotrophoblasts have maintained an abnormally high level of PDGF beta receptor expression, we propose that a deregulated PDGF autostimulatory loop is involved in the genesis of human choriocarcinoma from hydatidiform moles.
Institute for Experimental Drug Research, Karolinska Hospital, Stockholm, Sweden.
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L
Holmgren
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F
Flam
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E
Larsson
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R
Ohlsson
D002822:Choriocarcinoma / Q000737:chemistry* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006828:Hydatidiform Mole / Q000737:chemistry* / Q000235:genetics; D017403:In Situ Hybridization; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000235:genetics; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis*; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000235:genetics
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017479:Receptors, Platelet-Derived Growth Factor