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Open Access 01-10-2015 | Preclinical study

Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development

Authors: Sreeraj G. Pillai, Nupur Dasgupta, Chidananda M. Siddappa, Mark A. Watson, Timothy Fleming, Kathryn Trinkaus, Rebecca Aft

Published in: Breast Cancer Research and Treatment | Issue 3/2015

Abstract

The presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients is prognostic for early relapse. In the present study, we analyzed the gene expression profiles from BM cells of breast cancer patients to identify molecular signatures associated with DTCs and their relevance to metastatic outcome. We analyzed BM from 30 patients with stage II/III breast cancer by gene expression profiling and correlated expression with metastatic disease development. A candidate gene, PITX2, was analyzed for expression and phenotype in breast cancer cell lines. PITX2 was knocked down in the MDAMB231 cell lines for gene expression analysis and cell invasiveness. Expression of various signaling pathway molecules was confirmed by RT–PCR. We found that the expression of Paired-like Homeobox Transcription factor-2 (PITX2) is absent in the BM of normal healthy volunteers and, when detected in the BM of breast cancer patients, is significantly correlated with early metastatic disease development (p = 0.0062). Suppression of PITX2 expression significantly reduced invasiveness in MDAMB231 cells. Three genes—NKD1, LEF1, and DKK4—were significantly downregulated in response to PITX2 suppression. Expression of PITX2 in BM of early-stage breast cancer patients is associated with risk for early disease recurrence. Furthermore, PITX2 likely plays a role in the metastatic process through its effect on the expression of genes associated with the Wnt/beta-Catenin signaling pathway.

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Title: Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development
Authors: Sreeraj G. Pillai
Nupur Dasgupta
Chidananda M. Siddappa
Mark A. Watson
Timothy Fleming
Kathryn Trinkaus
Rebecca Aft
Publication date: 01-10-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3576-z

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