Nuclear factor-κB is central to the expression of truncated neurokinin-1 receptor in breast cancer: Implication for breast cancer cell quiescence within bone marrow stroma

Shakti H. Ramkissoon, Prem S. Patel, Marcelo Taborga, Pranela Rameshwar

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Breast cancer is a leading cause of mortality among women in the United States. Tac1 and neurokinin-1 (NK1) are involved in autocrine stimulation of breast cancer cells (BCCs). The single NK1 gene produces full-length (NK1-FL) and truncated (NK1-Tr) forms. NK1-Tr mediates malignancy in breast cells. We now report a critical role for nuclear factor-κN (NF-κB) in the expression of NK1-Tr, but not NK1-FL, in human BCCs. By Western and Northern blot analyses, NK1-FL and NK1-Tr were coexpressed in BCCs but were undetectable in nontumorigenic cells. Loss of repressive activity within the 5′ flanking region of the NK1 partly accounts for constitutive expression of NK1 in BCCs but could not account for the presence of NK1-Tr. Transient transfections with dominant-negative and wildtype IκB show that activation of NF-κB is required for the expression of NK1-Tr. Tac1 gene was linked to the generation of NK1-Tr because its overexpression in BCCs led to the production of multiple cytokines that can activate NF-κB to mediate NK1-Tr expression. Studies with Tac1 knockdown BCCs and Tac1-expressing nontumorigenic breast cells verified a role for NF-κB in the expression of NK1-Tr. The quiescent phenotype of BCCs on contact with bone marrow stroma was partly explained by decreased NF-κB activation and undetectable NK1-Tr. In summary, this study shows a role for NF-κB in the expression of NK1-Tr in BCCs, which seems to be reversed by bone marrow stromal cells.

Original languageEnglish (US)
Pages (from-to)1653-1659
Number of pages7
JournalCancer Research
Volume67
Issue number4
DOIs
StatePublished - Feb 15 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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