Nabiha Bashir1, Mehreen Ishfaq1, Kehkashan Mazhar2, Jahangir Sarwar Khan3, Ramla Shahid4. 1. Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan. 2. Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital Islamabad, Islamabad, Pakistan. 3. Department of General Surgery, Rawalpindi Medical University, Rawalpindi, Pakistan. 4. Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan. ramla_shahid@comsats.edu.pk.
Abstract
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.
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.
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