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

• Published in: Molecular and cellular endocrinology 2000-04, Vol.162 (1), p.151-156
• Main Authors: Ohkubo, Takao, Ohkura, Naganari, Maruyama, Kouji, Sasaki, Kazuki, Nagasaki, Koichi, Hanzawa, Hiroaki, Tsukada, Toshihiko, Yamaguchi, Ken
• Format: Article
• Language: English
• Subjects: A23187; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Base Sequence; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Calcimycin - pharmacology; cAMP response element; Cyclic AMP Response Element-Binding Protein - metabolism; DNA, Neoplasm - genetics; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Female; Humans; Ionophores - pharmacology; Molecular Sequence Data; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neuron-derived orphan receptor; Phosphorylation; Promoter Regions, Genetic - drug effects; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Steroid; Receptors, Thyroid Hormone; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Signal Transduction; Tumor Cells, Cultured
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(00)00222-7

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.