Regulation of the ectopically expressed human glycoprotein alpha-subunit gene in the human hepatoma cell line NPLC
Autor: | Laura B. Rosen, Gail K. Adler, Zoya K. Arbiser, Camilo Martinez, Jack L. Arbiser, Joseph A. Majzoub |
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Rok vydání: | 1994 |
Předmět: |
Transcriptional Activation
medicine.medical_specialty Carcinoma Hepatocellular Transcription Genetic Biology Second Messenger Systems Dexamethasone Cell Line Endocrinology Transcription (biology) Internal medicine Gene expression Tumor Cells Cultured medicine Humans Hydroxyurea RNA Messenger Protein Kinase C G alpha subunit Regulation of gene expression chemistry.chemical_classification Messenger RNA Colforsin Liver Neoplasms Gene Expression Regulation Neoplastic Kinetics Methotrexate chemistry Glycoprotein Hormones alpha Subunit Cell culture Second messenger system Tetradecanoylphorbol Acetate Glycoprotein hormones hormone substitutes and hormone antagonists |
Zdroj: | Endocrinology. 134:582-587 |
ISSN: | 1945-7170 0013-7227 |
DOI: | 10.1210/endo.134.2.7507828 |
Popis: | 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. |
Databáze: | OpenAIRE |
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