Differential expression of human placental growth hormone variant and chorionic somatomammotropin genes in choriocarcinoma cells treated with methotrexate.
Chorionic somatomammotropin (hCS) genes (hCS-A and hCS-B) and the placental growth hormone variant (hGH-V) gene are expressed in the syncytiotrophoblast in vivo, and at low levels in cytotrophoblast-like choriocarcinoma (BeWo) cells. Treatment of choriocarcinoma cells with methotrexate (MTX) will induce a cell type intermediate between a cytotrophoblast and syncytiotrophoblast. After treatment with MTX, hCS/hGH-V mRNA levels were decreased in BeWo cells, and only hGH-V and minor hCS-A related transcripts of 1.6, 2.1 and 4.2 kilobases, termed hCS-A2, hCS-A3 and hCS-A4, respectively, were detected. By contrast, chorionic gonadotropin RNA levels were increased. This pattern of hCS/hGH-V expression resembles that observed when BeWo cells are grown in thyroid hormone (T3)-depleted serum, where hGH-V/hCS RNA increases in response to T3. This increase is blunted by MTX treatment, but is not due to a decrease in number or affinity of T3 receptors. These data indicate that the hGH-V and hCS genes can be differentially regulated by MTX, and are consistent with MTX interfering with T3 responsiveness of these genes. Also, if BeWo cells treated with MTX do represent a transitional state, these data raise the possibility that hGH-V and hCS possess a different temporal pattern of expression in the developing trophoblast.
Nickel
B E
BE
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Bock
M E
ME
Nachtigal
M W
MW
Cattini
P A
PA
D000199:Actins / Q000235:genetics; D001483:Base Sequence; D002822:Choriocarcinoma / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000235:genetics; D015342:DNA Probes; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010926:Placental Hormones / Q000235:genetics*; D010928:Placental Lactogen / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism
D000199:Actins; D006063:Chorionic Gonadotropin; D015342:DNA Probes; C064980:GH2 protein, human; D010926:Placental Hormones; D012333:RNA, Messenger; D014284:Triiodothyronine; D013006:Growth Hormone; D010928:Placental Lactogen; D008727:Methotrexate