Early induction of the orphan nuclear receptor NOR-1 during cell death of the human breast cancer cell line MCF-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.
Ohkubo
T
T
Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.
Ohkura
N
N
Maruyama
K
K
Sasaki
K
K
Nagasaki
K
K
Hanzawa
H
H
Tsukada
T
T
Yamaguchi
K
K
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000001:Calcimycin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D007476:Ionophores; C490412:NR4A3 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D000001:Calcimycin