Differential expression and tumorigenic function of neurotensin receptor 1 in neuroendocrine tumor cells

Ji Tae Kim, Jing Li, Jun Song, Eun Y. Lee, Heidi L. Weiss, Courtney M. Townsend, B. Mark Evers

    Research output: Contribution to journalArticle

    15 Scopus citations

    Abstract

    Neurotensin (NTS), localized predominantly to the small bowel, stimulates the growth of a variety of cancers, including neuroendocrine tumors (NETs), mainly through its interaction with the high-affinity NTS receptor 1 (NTSR1). Here, we observed increased expression of NTSR1 in almost all tested clinical NET samples, but not in normal tissues. Through RT-PCR analysis, we found that the expression of NTSR1 and NTSR2 was either variable (NTSR1) or absent (NTSR2) in human NET cell lines. In contrast, NTSR3 and NTS were expressed in all NET cells. Treatment with 5-aza-2'-deoxycytidine, a demethylating agent, increased levels of NTSR1 and NTSR2 suggesting that DNA methylation contributes to NTSR1/2 expression patterns, which was confirmed by methylation analyses. In addition, we found that knockdown of NTSR1 decreased proliferation, expression levels of growth-related proteins, and anchorage-independent growth of BON human carcinoid cells. Moreover, stable silencing of NTSR1 suppressed BON cell growth, adhesion, migration and invasion. Our results show that high expression of NTSR1 is found in clinical NETs and that promoter methylation is an important mechanism controlling the differential expression of NTSR1 and silencing of NTSR2 in NET cells. Furthermore, knockdown of NTSR1 in BON cells suppressed oncogenic functions suggesting that NTSR1 contributes to NET tumorigenesis.

    Original languageEnglish (US)
    Pages (from-to)26960-26970
    Number of pages11
    JournalOncotarget
    Volume6
    Issue number29
    DOIs
    StatePublished - 2015

    Keywords

    • Cell growth
    • Cell migration
    • Neuroendocrine tumor
    • Neurotensin receptor 1
    • Promoter methylation

    ASJC Scopus subject areas

    • Oncology

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