Calcitonin increases transcription of parathyroid hormone-related protein via cAMP

Autor: P. J. Chilco, S.J. Kaczmarczyk, V. Leopold, S. Chu, Jeffrey D Zajac, J.M. Gerardi
Rok vydání: 1993
Předmět:
Calcitonin
medicine.medical_specialty
Lung Neoplasms
Transcription
Genetic

Recombinant Fusion Proteins
Response element
Molecular Sequence Data
Biology
Calcitonin gene-related peptide
Regulatory Sequences
Nucleic Acid

Biochemistry
Second Messenger Systems
chemistry.chemical_compound
Endocrinology
Internal medicine
1-Methyl-3-isobutylxanthine
medicine
Transcriptional regulation
Cyclic AMP
Tumor Cells
Cultured

Humans
RNA
Messenger

RNA
Neoplasm

Calcitonin receptor
Molecular Biology
Regulation of gene expression
Forskolin
Parathyroid hormone-related protein
Base Sequence
Ionomycin
Colforsin
Parathyroid Hormone-Related Protein
Proteins
Molecular biology
Neoplasm Proteins
Gene Expression Regulation
Neoplastic

chemistry
Bucladesine
Protein Biosynthesis
hormones
hormone substitutes
and hormone antagonists
Zdroj: Molecular and cellular endocrinology. 94(1)
ISSN: 0303-7207
Popis: Transcriptional regulation of the human parathyroid hormone-related protein (PTHrP) gene by calcitonin was examined in a lung cancer line (BEN cells). Northern analysis demonstrated that calcitonin caused a rapid 4.5-fold elevation in PTHrP mRNA. Transient transfection of a construct containing 1119 base pairs of the human PTHrP gene 5' to the ATG start site of translation, fused to the CAT reporter sequence, was used to demonstrate a five-fold increase in transcription by calcitonin. Similar increases were also observed when transfected cells were exposed to a number of cAMP agonists including forskolin, as well as isobutyl-methylxanthine. A putative cAMP responsive element (5'-TGACTTCA-3') present within exon 4 was placed upstream of the heterologous SV40 promoter. Expression of this construct was elevated 4.5-fold in response to calcitonin and 7-fold in response to forskolin. Similar responses to calcitonin occurred with a smaller construct (pZMR30) containing 530 bp of sequence upstream of the ATG start site. Thus we postulate that calcitonin acts at least partially via cAMP through this element in exon 4 of the human PTHrP gene.
Databáze: OpenAIRE