Regulation of the ectopically expressed human glycoprotein alpha-subunit gene in the human hepatoma cell line NPLC.
The human glycoprotein alpha-subunit is the common subunit of the heterodimeric hormones CG (hCG), TSH, LH, and FSH. Human glycoprotein alpha-subunit is produced eutopically in placenta, pituitary, and choriocarcinoma and ectopically in a large variety of human tumors. We report ectopic glycoprotein alpha-subunit messenger RNA (mRNA) and peptide production in the human hepatoma cell line, NPLC. Neither hCG beta mRNA nor intact hCG peptide was detected. Antimetabolite regulation of glycoprotein alpha-subunit expression in NPLC cells resembled that found in choriocarcinoma cells in that it was stimulated by hydroxyurea. In addition, glycoprotein alpha-subunit mRNA expression and transcription in NPLC were stimulated by activators of the protein kinase A and C second messenger pathways, as well as by glucocorticoid. Glucocorticoid augmented glycoprotein alpha-subunit gene transcription by phorbol ester and forskolin, in contrast to its simultaneous inhibitory effect on phorbol ester activation of the CRH gene, which is also ectopically expressed in these cells. Glucocorticoid thus modulates the activation of these genes by phorbol ester in opposite directions, despite their identical cellular context. The NPLC cell line provides a new model for the study of human glycoprotein alpha-subunit gene regulation and free glycoprotein alpha-subunit secretion. In addition, it should be useful for investigating the role that specific cis-acting DNA sequences play in glucocorticoid modulation of gene induction by second messenger pathways.
Arbiser
J L
JL
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Martinez
C
C
Arbiser
Z K
ZK
Adler
G K
GK
Rosen
L B
LB
Majzoub
J A
JA
D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D008113:Liver Neoplasms; D008727:Methotrexate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015290:Second Messenger Systems / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D015292:Glycoprotein Hormones, alpha Subunit; D012333:RNA, Messenger; D005576:Colforsin; D003907:Dexamethasone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D006918:Hydroxyurea; D008727:Methotrexate