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

Mol Cell Endocrinol. 2000 Apr 25;162(1-2):151-6. 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.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Base Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Calcimycin / pharmacology
  • 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
  • Phosphorylation
  • Promoter Regions, Genetic / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Signal Transduction
  • Tumor Cells, Cultured


  • 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