Early induction of the orphan nuclear receptor NOR-1 during cell death of the human breast cancer cell line MCF-7.

Abstract

The neuron-derived orphan receptor (NOR-1) is a member of the NGFI-B subfamily within the nuclear receptor superfamily. In T-cell apoptosis, where NGFI-B plays an essential role, a functional redundancy between NGFI-B and NOR-1 has been demonstrated. Here, we examined the regulation and expression of the NOR-1 gene during cell death induced by a calcium ionophore A23187 in the human breast cancer cell line MCF-7. A23187 caused a transient increase in NOR-1 mRNA levels within 6 h after treatment. To delineate the sequences required for the transitional response to A23187, a series of promoter deletion mutants were constructed. From the transient transfection experiments, the element responsive to A23187 was identified between -94 and -42 base pairs upstream from the transcription initiation site. This 53-base pairs region contains three copies of the cAMP response element (CRE). Furthermore, phosphorylation of the CRE-binding protein (CREB), which affects the transcription of the CRE dependent-genes, was detected 30 min after A23187 stimulation. Our findings are consistent with NOR-1 involvement in A23187-induced cell death via the CRE-CREB signaling pathway.

• Authors: T Ohkubo, N Ohkura, K Maruyama, K Sasaki, K Nagasaki, H Hanzawa, T Tsukada, K Yamaguchi
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 162 Issue 1-2 Pg. 151-6 (Apr 25 2000) ISSN: 0303-7207 [Print] Ireland
• PMID: 10854708 (Publication Type: Journal Article)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• DNA, Neoplasm
• DNA-Binding Proteins
• Ionophores
• NR4A3 protein, human
• Nerve Tissue Proteins
• RNA, Messenger
• RNA, Neoplasm
• Receptors, Cytoplasmic and Nuclear
• Receptors, Steroid
• Receptors, Thyroid Hormone
• Calcimycin

Topics

• Apoptosis (drug effects, physiology)
• Base Sequence
• Breast Neoplasms (genetics, metabolism, pathology)
• Calcimycin (pharmacology)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• DNA, Neoplasm (genetics)
• DNA-Binding Proteins (biosynthesis, genetics)
• Female
• Humans
• Ionophores (pharmacology)
• Molecular Sequence Data
• Nerve Tissue Proteins (biosynthesis, genetics)
• Phosphorylation
• Promoter Regions, Genetic (drug effects)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Receptors, Cytoplasmic and Nuclear (biosynthesis, genetics)
• Receptors, Steroid
• Receptors, Thyroid Hormone
• Signal Transduction
• Tumor Cells, Cultured