REGULATION OF THE ECTOPICALLY EXPRESSED HUMAN GLYCOPROTEIN ALPHA-SUBUNIT GENE IN THE HUMAN HEPATOMA-CELL LINE NPLC

The human glycoprotein oc-subunit is the common subunit of the heterod imeric hormones CG (hCG), TSH, LH, and FSH. Human glycoprotein alpha-s ubunit is produced eutopically in placenta, pituitary, and choriocarci noma and ectopically in a large variety of human tumors. We report ect opic glycoprotein alpha-subunit messenger RNA (mRNA) and peptide produ ction in the human hepatoma cell line, NPLC. Neither hCG beta mRNA nor intact hCG peptide was detected. Antimetabolite regulation of glycopr otein alpha-subunit expression in NPLC cells resembled that found in c horiocarcinoma cells in that it was stimulated by hydroxyurea. In addi tion, glycoprotein alpha-subunit mRNA expression and transcription in NPLC were stimulated by activators of the protein kinase A and C secon d messenger pathways, as well as by glucocorticoid. Glucocorticoid aug mented glycoprotein alpha-subunit gene transcription by phorbol ester and forskolin, in contrast to its simultaneous inhibitory effect on ph orbol ester activation of the CRH gene, which is also ectopically expr essed in these cells. Glucocorticoid thus modulates the activation of these genes by phorbol ester in opposite directions, despite their ide ntical cellular context. The NPLC cell line provides a new model for t he 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 pla y in glucocorticoid modulation of gene induction by second messenger p athways.