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-I) is a member of the NGFI-B subfam ily within the nuclear receptor superfamily. In T-cell apoptosis, where NGF I-B plays an essential role, a functional redundancy between NGFI-B and NOR -I has been demonstrated. Here, we examined the regulation and expression o f 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 increas e in NOR-I mRNA levels within 6 h after treatment. To delineate the sequenc es required for the transitional response to A23187, a series of promoter d eletion mutants were constructed. From the transient transfection experimen ts, the element responsive to A23187 was identified between - 94 and - 42 b ase pairs upstream from the transcription initiation site. This 53-base pai rs region contains three copies of the cAMP response element (CRE). Further more, 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-i nduced cell death via the CRE-CREB signaling pathway. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.