Expression of neurotensin and NT1 receptor in human breast cancer: A potential role in tumor progression

Frédérique Souazé, Sandra Dupouy, Véronique Viardot-Foucault, Erik Bruyneel, Samir Attoub, Christian Gespach, Anne Gompel, Patricia Forgez

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.

Original languageEnglish
Pages (from-to)6243-6249
Number of pages7
JournalCancer Research
Volume66
Issue number12
DOIs
Publication statusPublished - Jun 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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