The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells depends on the relative degree of invasive and metastatic potential

Castro, Tammy; Cohen, Marion C.; Rameshwar, Pranela

doi:10.1007/s10585-006-9001-6

Cited by 34 publications

(30 citation statements)

References 27 publications

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“…Such knowledge could carry importance in a clinical setting, for example, to predict either prognosis and/or a treatment response with NK1R antagonists. Such a correlation has been described for the expression rate of the SP/NK1R complex and prognosis in other pediatric tumors (110,(152)(153)(154). For example, Garcia-Recio et al found that SP contributes to persistent transmodulation of the ErbB receptors, EGFR and HER2, in breast cancer, where it enhances malignancy and therapeutic resistance (110).…”

Section: The Nk1r As An Anti-tumor Target In Hepatoblastoma In the CLmentioning

confidence: 85%

Therapeutic Innovations for Targeting Hepatoblastoma

Garnier

Ilmer

Kappler

et al. 2016

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Section: The Nk1r As An Anti-tumor Target In Hepatoblastoma In the CLmentioning

confidence: 85%

Therapeutic Innovations for Targeting Hepatoblastoma

Garnier

Ilmer

Kappler

et al. 2016

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“…It has previously been proposed that a correlation exists between the expression rate of the NK1R/SP complex and prognosis in various types of cancer (18)(19)(20)(21)(22). Garcia-Recio et al identified that SP contributes to persistent transmodulation of the ErbB receptors, epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2), in breast cancer, acting to enhance malignancy and therapeutic resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, this signature discriminates invasive and metastatic from localized HB and predicts prognosis with high accuracy (16). Additionally, it has recently been suggested that the expression of TACR1 may correlate with a clinically worse prognosis in some cancers (18)(19)(20)(21)(22). However, scientific evidence for such an association remains scarce.…”

Section: Introductionmentioning

confidence: 99%

Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

et al. 2015

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Abstract. The substance P (SP; also known as TAC1)/neurokinin-1 receptor (NK1R; also known as TACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription-quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1 (fl-TACR1) and truncated-TACR1 (tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality, CTNNB1 mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characteri zing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressed TACR1 significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1 correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1 correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1 and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1 is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr-TACR1 is expressed ubiquitously among the different subsets of HB. Therefore, NK1R may serve as a potent anticancer target in a large variety of patients with HB, independent of tumor biology and clinical stage.

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“…The Tac1 gene produces several peptides belonging to the tachykinin family, of which substance P and neurokinin-A are its major products (9,10). In most peripheral cells, including breast epithelial cells, substance P and neurokinin-A interact with the seven-transmembrane, G protein -coupled receptors neurokinin-1 and neurokinin-2 (11,12). In nontransformed cells, neurokinin-1 and neurokinin-2 exhibit intracellular cross-talk so that each regulates the biological effects of the other (13).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Factor-κB Accounts for the Repressor Effects of High Stromal Cell–Derived Factor-1α Levels on Tac1 Expression in Nontumorigenic Breast Cells

Corcoran¹,

Rameshwar

2007

Molecular Cancer Research

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Stromal cell -derived factor-1A (SDF-1A) is a CXC chemokine that interacts with CXCR4 receptor. Tac1 encodes peptides belonging to the tachykinins, including substance P. SDF-1A production is decreased in Tac1 knockdown breast cancer cells and is also reduced in these cancer cells following contact with bone marrow stroma when Tac1 expression is increased. Here, we report on the effects of relatively high and low SDF-1A levels on Tac1 expression in nontumorigenic breast cells MCF12A. Reporter gene assays, Northern analyses, and ELISA for substance P showed increased Tac1 expression at 20 and 50 ng/mL SDF-1A and reduced expression at 100 ng/mL. Omission of the untranslated region showed a dose-dependent effect of SDF-1A on reporter gene activity, suggesting that receptor desensitization cannot account for the suppressive effects at 100 ng/mL SDF-1A. Tac1 expression at high SDF-1A involves an intracellular signaling pathway that incorporates the activation of phosphatidylinositol 3-kinase-phosphoinositidedependent kinase-1-AKT-nuclear factor-KB (NF-KB). The major repressive effect occurs via NF-KB located within exon 1. In summary, NF-KB is involved in the repression of Tac1 at higher levels of SDF-1A in MCF12A. These results are relevant to dysfunction of Tac1 in breast cancer cells and also provide insights on the behavior of breast cancer cells as they traverse across gradient changes of SDF-1A. (Mol Cancer Res 2007;5(4):373 -81)

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The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells depends on the relative degree of invasive and metastatic potential

Cited by 34 publications

References 27 publications

Therapeutic Innovations for Targeting Hepatoblastoma

Therapeutic Innovations for Targeting Hepatoblastoma

Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

Nuclear Factor-κB Accounts for the Repressor Effects of High Stromal Cell–Derived Factor-1α Levels on Tac1 Expression in Nontumorigenic Breast Cells

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