Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development
| Autor: | Timothy P. Fleming, Sreeraj G. Pillai, Rebecca Aft, Mark A. Watson, Chidananda M. Siddappa, Kathryn Trinkaus, Nupur Dasgupta |
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| Jazyk: | angličtina |
| Předmět: |
Candidate gene
Cancer Research Gene Expression Bone Neoplasms Breast Neoplasms Biology Metastasis Twist transcription factor Preclinical Study Breast cancer Bone Marrow Cell Line Tumor Gene expression Biomarkers Tumor medicine Humans Neoplasm Invasiveness PITX2 Neoplasm Staging Homeodomain Proteins Twist-Related Protein 1 Wnt signaling pathway Nuclear Proteins medicine.disease Wnt signaling Invasiveness Gene Expression Regulation Neoplastic Gene expression profiling Phenotype medicine.anatomical_structure Oncology Case-Control Studies Gene Knockdown Techniques Disease Progression Cancer research Female Disseminated tumor cells Bone marrow Neoplasm Recurrence Local Follow-Up Studies Transcription Factors |
| Zdroj: | Breast Cancer Research and Treatment |
| ISSN: | 0167-6806 |
| DOI: | 10.1007/s10549-015-3576-z |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1007/s10549-015-3576-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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