Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 153, Issue 3, Pages 507-517Publisher
SPRINGER
DOI: 10.1007/s10549-015-3576-z
Keywords
Breast cancer; Disseminated tumor cells; Gene expression; Metastasis; PITX2; Wnt signaling; Invasiveness
Categories
Funding
- NCATS NIH HHS [UL1 TR001425] Funding Source: Medline
- NCI NIH HHS [R01 CA172623, P30 CA091842] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available