NTR1: A key neuropeptide receptor in cancer and inflammatory signaling

• Gene Information: Neurotensin receptor 1 (NTR1, also known as NTSR1) is a protein-coding gene located on chromosome 20q13.33. It encodes a high-affinity G protein-coupled receptor (GPCR) for the neuropeptide neurotensin (NTS), and belongs to the class A rhodopsin-like GPCR family.
• Protein Expression: NTR1 is expressed in both the central nervous system and peripheral tissues, including the gastrointestinal tract, pancreas, lung, and immune-related tissues. It is frequently overexpressed in several cancers, where it contributes to tumor growth and metastasis.
• Signaling Pathway：NTS binding to NTR1 activates several key downstream signaling pathways involved in tumor progression and inflammation. These pathways mainly include: small GTPase Pathway, Ca²⁺ Mobilization Pathway, and PKC/ERK Signaling Pathway.
• Therapeutic Inhibition: Targeting NTR1 with antagonists, antibody-drug conjugates, or radioligand therapies can inhibit tumor progression and inflammation-related signaling, demonstrating therapeutic potential in cancer treatment.

NTR1

• Exon 1 (partly) and exons 2–4 of the mouse NTR1 gene that encode the entire protein (from ATG to stop codon), including 3’UTR are replaced with the corresponding human sequences in B-hNTR1 mice.
• The endogenous mouse promoter, and 5′ UTR regions are retained, allowing human NTR1 expression to be driven by the native mouse NTR1 promoter, while endogenous mouse NTR1 transcription and translation are abolished.

• Human NTR1 is specifically and correctly expressed in B-hNTR1 Mice.

Strain specific analysis of NTR1 mRNA expression in wild-type C57BL/6 mice and B-hNTR1 Mice by RT-PCR. Brain RNA was isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hNTR1 mice (H/H), and then cDNA libraries were synthesized by reverse transcription, followed by PCR with human NTR1 primers. Human NTR1 mRNA was exclusively detectable in homozygous B-hNTR1 mice but not in wild-type mice.