Regulatory role of hepatocyte nuclear factor-4alpha on gastric choriocarcinoma function.
Gastric choriocarcinoma is a highly aggressive carcinoma, most probably originating from somatic cells in the gastric mucosal layer. We herein investigated the regulatory role of hepatocyte nuclear factor (HNF)-4alpha, a transcriptional regulator expressed in non-neoplastic and neoplastic gastric tissues, on functions of gastric choriocarcinoma cells. HNF-4alpha cDNA was stably transfected to a gastric choriocarcinoma cell line, SCH. Alterations in SCH cell functions such as histology, ultrastructure, proliferation, production of trophoblast-specific proteins, and chemosensitivity to methotrexate (MTX) were examined. Neither in vitro and in vivo proliferations nor HLA-G expression differed significantly between the mock-transfected and HNF-4alpha-transfected SCH cells, while suppressed human chorionic gonadotropin (hCG) secretions, increased human placental lactogen (hPL) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) immunoreactivity, and decreased chemosensitivity to MTX were seen in HNF-4alpha-transfected SCH cells. General histologic features in xenograft nodules were unaltered, but, ultrastructurally, fascicles of paranuclear filaments were significantly more numerous in HNF-4alpha-transfected SCH cells. These results indicated an HNF-4alpha-rendered functional regulation in SCH cells, suggesting a role of transcriptional factors abundant in gastric but not in trophoblastic tissues/cells on the functional modulation of gastric choriocarcinoma cells.
Department of Molecular Pathology, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-Ku, Chiba 260-8670, Japan.
Naobumi
N
Tochigi
Takashi
T
Kishimoto
Takahito
T
Suyama
Yuichiro
Y
Nagai
Takashi
T
Nikaido
Bunshiro
B
Akikusa
Eric
E
Virtudazo
Masashi
M
Yamaguchi
Hiroshi
H
Ishikura
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D031954:Choriocarcinoma, Non-gestational / Q000378:metabolism* / Q000556:secondary; D006063:Chorionic Gonadotropin / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism; D059951:HLA-G Antigens; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010928:Placental Lactogen / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006063:Chorionic Gonadotropin; D006680:HLA Antigens; D059951:HLA-G Antigens; D051557:Hepatocyte Nuclear Factor 4; D015395:Histocompatibility Antigens Class I; D010928:Placental Lactogen; D008727:Methotrexate