ABSTRACT
The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments.
Subject(s)
Breast Neoplasms , Age of Onset , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carrier Proteins , Female , Glycolysis/genetics , Hexokinase , Humans , Membrane Proteins , Neoplasm Metastasis , Pakistan , Phosphofructokinase-1, Muscle Type/metabolism , Thyroid Hormones , Thyroid Hormone-Binding ProteinsABSTRACT
BACKGROUND: Biological treatment of many cancers currently targets membrane bound receptors located on a cell surface. We are in a great to need identify novel membrane proteins associated with migration and metastasis of breast cancer cells. CD271, a single transmembrane protein belongs to tumor necrosis factor receptor family acts and play its role in proliferation of cancer cell. The purpose of this study is to investigate the role of CD271 in breast cancer. METHODS AND RESULTS: In this study we analyzed the mRNA expression of CD271 in breast tumor tissue, breast cancer cell line MCF7 and isolated cancer stem cells (MCF7-CSCs) by RT-qPCR. We also measured the protein levels through western blotting in MCF-7 cell line. CD271 was upregulated in breast cancer patients among all age groups. Within the promoter region of CD271, there is a binding site for NF-κB1 which overlaps a putative quadraplex forming sequence. While CD271 also activates NF-κB pathway, down regulation of CD271 through quadraplex targeting resulted in inhibition of NF-κB and its downstream targets Nanog and Sox2. CONCLUSION: In conclusion, our data shows that CD271 and NF-κB are regulated in interdependent manner. Upon CD271 inhibition, the NF-κB expression also reduces which in turn affects the cell proliferation and migration. These results suggest that CD271 is playing a crucial rule in cancer progression by regulating NF-κB and is a good candidate for the therapeutic targeting.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , NF-kappa B/metabolism , Nerve Tissue Proteins/genetics , Receptors, Nerve Growth Factor/genetics , Signal Transduction , Transcriptome , Biopsy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Line, Tumor , Computational Biology/methods , Female , Gene Expression Profiling , Humans , Ligands , Models, Biological , Protein BindingABSTRACT
The main purpose of this study was to evaluate the association between reduction in XRCC2 gene and involvement of lymph node metastasis in breast cancer. In first part of the study, meta-analysis of 14 published XRCC2 studies was performed to define the role of XRCC2 gene as diagnostic marker and in second part of the study XRCC2 gene expression was observed using real time PCR in study cohort of 100 females (50 breast cancer patients and 50 controls). A statistically significant down regulation of XRCC2 (p < 0.04) and up-regulation of ki-67 (p < 0.05) was observed in breast cancer tissues compared to non-cancerous healthy tissues. In order to explore gene-gene and gene-clinicopathological parameters relationship Spearmen correlation was performed. We observed a significantly negative correlation between XRCC2 and Ki-67 expression (r = -0.376**, p < 0.01). In case of gene-clinicopathological parameters relationship, we observed a significant correlation between XRCC2 expression and lymph node status (r = -0.521***, p < 0.002) and metastatic status (r = -0.303*, p < 0.04) of breast cancer patients. Our data suggests that deregulation of XRCC2 in breast cancer has the potential to predict lymph node metastasis and may serve as a therapeutic target for breast cancer patients at risk of metastasis.
