ABSTRACT
Breast cancer (BC) remains a significant threat to the health of women; however, the mechanism underlying the initiation and progression of BC is poorly understood. We analyzed data from the Gene Expression Omnibus database and The Cancer Genome Atlas datasets to identify differentially expressed genes between BC and normal tissues. The roles of dCTP pyrophosphatase 1 (DCTPP1) and quinolinate phosphoribosyltransferase (QPRT) in BC cells were investigated after knocking down or overexpressing the genes. The regulatory effects of Down syndrome cell adhesion molecule antisense RNA 1 (DSCAM-AS1) on DCTPP1 and QPRT expression were determined using luciferase reporter, RNA immunoprecipitation, RNA pull-down, chromatin immunoprecipitation, and fluorescence in situ hybridization assays. DCTPP1 and QPRT were overexpressed in BC compared to normal tissues. Overexpression of DCTPP1 and QPRT was associated with poor BC progression and promoted growth, migration, and invasion of MCF7 and T47D cells but inhibited apoptosis. DSCAM-AS1 increased QPRT expression via competitively binding miRNA-150-5p and miRNA-2467-3p. DSCAM-AS1 promoted DCTPP1 gene transcription by affecting H3K27 acetylation and enhanced DCTPP1 mRNA stability by binding to the 3' untranslated region, which collectively resulted in DCTPP1 overexpression. Overall, DSCAM-AS1 knockdown decreased both DCTPP1 and QPRT expression, inhibiting the growth, migration, and invasion of estrogen receptor-positive BC.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/therapy , Pentosyltransferases/genetics , Pyrophosphatases/genetics , RNA, Long Noncoding/therapeutic use , Receptors, Estrogen/metabolism , Adult , Aged , Apoptosis/genetics , Cell Line, Tumor , Disease Progression , Down Syndrome/genetics , Down-Regulation , Female , Gene Silencing , Histones/metabolism , Humans , MicroRNAs/genetics , Middle Aged , RNA, Long Noncoding/geneticsABSTRACT
Objective: To investigate the effect of HOXD3 expression on the stem cell-like characteristics of breast cancer cells and the relationship between HOXD3 expression and multi-drug resistance in breast cancer cells. Methods: From January 2006 to December 2008, 87 specimens of breast cancer patients from the Affiliated Tumor Hospital of Harbin Medical University were collected. The ex-pression of HOXD3 in breast cancer cells and tissues was detected by immunohistochemical staining method. The expression levels of HOXD3 in CDDP or DOX-resistant cell lines MDA-MB-231 and MDA-MB-435 were detected by RT-PCR, Western blot and immunofluo-rescence staining. The effect of HOXD3 overexpression on the expression levels of stem cell biomarkers in breast cancer cell lines MDA-MB-231 and MDA-MB-435 was analyzed. MTT assay and colony formation assay were used to demonstrate the role of HOXD3 in che-motherapy resistance of breast cancer cells. Results: The relative expression of HOXD3 mRNA in breast cancer was 4.16, which was sig-nificantly higher than 2.05 in normal tissues adjacent to cancer; the relative expression levels of HOXD3 mRNA in breast cancer cell lines MDA-MB-231, MDA-MBB-435 and MCF-7 were 3.25, 2.84 and 2.23, which were all higher than 1.00 in normal breast epithelial cell line MCF-10A ( all P＜0.05 ). The IC50s of MDA-MB-231 and MDA-MB-435 cell lines resistant to CDDP or DOX were (20.82±0.05) μmol/L, (19.69±0.47) μmol/L, (32.26±0.23) mmol/L and (26.08±0.55) mmol/L, respectively. Both were higher than the corresponding original cell lines (all P＜0.05), and the drug resistance times were 2.47 and 3.10 or 1.86 and 2.08, respectively. The number of tumor spheres and stem cell biomarker expression levels of MDA-MB-231 and MDA-MB-435 with HOXD3 overexpression were significantly in-creased (all P＜0.05). Conclusions: The expression of HOXD3 plays an important role in the maintenance of stem cell-like properties and drug resistance of breast cancer cells. The results of this study will help us better understand the complexity of breast cancer and pro-vide a theoretical basis for the development of targeted molecular therapy.
ABSTRACT
Objecive To explore the significance of RECK expression in breast cancer .Methods Im-munohistochemical staining was used to analyze RECK expression levels in patients with breast cancer .We com-pared these data with the clinicopathological features of these patients .Rseults Breast cancer patients with nega-tive RECK expression had significantly lower DFS and 5-year survival rates than patients with positive RECK expression.In addition,for node-negative breast cancer ,negative RECK expression indicated markedly unfavor -able survival rate than positive arm .Multivariate analysis further confirmed that RECK expression was an inde -pendent prognostic factor for patients with breast cancer .Conclusion The loss of RECK expression indicates un-favorable survival rate for patients with breast cancer .RECK expression is a new ,important risk factor for recur-rence in breast cancer .
ABSTRACT
Hox genes encode a family of homeodomain-containing transcription factors that determine cellular identity during development and which are also expressed in some types of cancer. The HOXD3 gene, a member of the Hox gene family, has been demonstrated to be expressed in several tumor cell lines, which exhibit enhanced invasion and metastasis through coordinate expression of metastasis-associated factors. However, the clinical impact of HOXD3 in breast cancer remains unclear. In the current study, we examined the expression of HOXD3 and integrin ß3 by immunohistochemical staining in patients with invasive breast cancer. We found that HOXD3 expression was significantly frequent in high histopathological grade and hormone-receptor negative breast cancer patients. The expression of HOXD3 was closely associated with integrin ß3 expression. Furthermore, patients with high HOXD3 expression levels in their breast tumors had significantly shorter survival times than patients in which HOXD3 was weakly expressed in breast tumors. Univariate and multivariate analyses confirmed that increased HOXD3-expression was an independent and significant factor in predicting poor prognosis for patients with breast cancer. In conclusion, HOXD3 expression is a significant unfavorable prognostic factor for patients with invasive breast cancer and as such is a potentially useful prognostic marker for breast cancer.
