Knockdown of LRP/LR Induces Apoptosis in breast and oesophageal cancer cells.

dc.contributor.authorKhumalo, T.
dc.contributor.authorFerreira, E.
dc.contributor.authorJovanovic, K.
dc.contributor.authorVeale, R.B.
dc.contributor.authorWeiss, S.F.T.
dc.description.abstractCancer is a global burden due to high incidence and mortality rates and is ranked the second most diagnosed disease amongst non-communicable diseases in South Africa. A high expression level of the 37kDa/67kDa laminin receptor (LRP/LR) is one characteristic of cancer cells. This receptor is implicated in the pathogenesis of cancer cells by supporting tumor angiogenesis, metastasis and especially for this study, the evasion of apoptosis. In the current study, the role of LRP/LR on cellular viability of breast MCF-7, MDA-MB 231 and WHCO1 oesophageal cancer cells was investigated. Western blot analysis revealed that total LRP expression levels of MCF-7, MDA-MB 231 and WHCO1 were significantly downregulated by targeting LRP mRNA using siRNA-LAMR1. This knockdown of LRP/LR resulted in a significant decrease of viability in the breast and oesophageal cancer cells as determined by an MTT assay. Transfection of MDA-MB 231 cells with esiRNA-RPSA directed against a different region of the LRP mRNA had similar effects on LRP/LR expression and cell viability compared to siRNA-LAMR1, excluding an off-target effect of siRNALAMR1. This reduction in cellular viability is as a consequence of apoptosis induction as indicated by the exposure of the phosphatidylserine protein on the surface of breast MCF-7, MDA-MB 231 and oesophageal WHCO1 cancer cells, respectively, detected by an Annexin-V/FITC assay as well as nuclear morphological changes observed post-staining with Hoechst. These observations indicate that LRP/LR is crucial for the maintenance of cellular viability of breast and oesophageal cancer cells and recommend siRNA technology targeting LRP expression as a possible novel alternative technique for breast and oesophageal cancer treatment.en_ZA
dc.description.sponsorshipThis work was supported by the National Research Foundation, the Republic of South Africa, the Republic of South Africa.en_ZA
dc.identifier.citationKhumalo, T. et al. 2015. Knockdown of LRP/LR Induces Apoptosis in breast and oesophageal cancer cells.PLoS ONE 10 (10): e0139584.en_ZA
dc.journal.titlePLoS ONEen_ZA
dc.rights© 2015 Khumalo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.subjectfluorescein isothiocyanate;en_ZA
dc.subjectlaminin receptor;en_ZA
dc.subjectlipocortin 5;en_ZA
dc.subjectmessenger RNA;en_ZA
dc.subjectsmall interfering RNA;en_ZA
dc.subjectcancer cell line;en_ZA
dc.subjectcell structure;en_ZA
dc.subjectcell surface;en_ZA
dc.subjectcell viability;en_ZA
dc.subjectcontrolled study;en_ZA
dc.subjectdown regulation;en_ZA
dc.subjectesophageal cancer cell line;en_ZA
dc.subjectprotein expression;en_ZA
dc.subjectbreast cancer cell line;en_ZA
dc.titleKnockdown of LRP/LR Induces Apoptosis in breast and oesophageal cancer cells.en_ZA
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