Targeting LRP/LR for the treatment of metastatic lung and colorectal cancer through impediment of telomerase activity

Simple item page
dc.contributor.authorBaichan, Pavan
dc.date.accessioned2019-04-05T11:53:09Z
dc.date.available2019-04-05T11:53:09Z
dc.date.issued2018
dc.descriptionA research report submitted in partial fulfilment to the degree of School of Molecule and Cell Biology, University of the Witwatersrand University of the Witwatersrand, Johannesburg, 2018
dc.description.abstractThe 37 kDa/67 kDa laminin receptor (LRP/LR) plays a vital role in the malignancy of various cancer types contributing to invasion, adhesion, apoptosis evasion, proliferation and tumour angiogenesis. In addition, LRP/LR interacts with the catalytic reverse transcriptase subunit, TERT, of the ribonucleoprotein telomerase. Both LRP/LR and telomerase are implicated in cancer progression and knockdown of LRP/LR causes a decrease in telomerase activity in breast cancer cells. In the current study, LRP/LR was downregulated in lung adenocarcinoma (A549) and late-stage colorectal carcinoma (DLD-1) cells in an attempt to impede telomerase activity and ultimately impede cancer progression. Western blotting analysis showed a significant decrease in LRP/LR levels in HEK293 (Human Embryonic Kidney Cells) and A549 cells after siRNA mediated LRP/LR knockdown. To confirm LRP/LR knockdown confocal microscopy was performed; a reduction in LRP/LR protein levels was observed which also resulted in a subsequent decrease in hTERT mRNA levels with a corresponding decrease in hTERT levels in HEK293, A549, and DLD-1 cell lines. Furthermore, siRNA mediated knockdown of LRP/LR significantly decreased telomerase activity in HEK293, A549, and DLD-1 cells. The effect of LRP/LR downregulation on cellular viability was investigated via the MTT assay and a significant decrease in cell viability in A549 and DLD-1 cells was observed. Since downregulation of LRP/LR impedes telomerase activity and decreases cell viability, siRNAs directed against LRP mRNA acts as potential alternative therapeutic tools for treatment of lung adenocarcinoma and late-stage colorectal carcinoma.en_ZA
dc.description.librarianXL2019en_ZA
dc.format.extentOnline resource (62 leaves)
dc.identifier.citationBaichan, Pavan (2018) Targeting LRP/LR for the treatment of metastatic lung and colorectal cancer through impediment of telomerase activity, University of the Witwatersrand, Johannesburg, https://hdl.handle.net/10539/26700
dc.identifier.urihttps://hdl.handle.net/10539/26700
dc.language.isoenen_ZA
dc.subject.lcshCancer cells
dc.subject.lcshLungs--Cancer
dc.subject.lcshSmall interfering RNA
dc.titleTargeting LRP/LR for the treatment of metastatic lung and colorectal cancer through impediment of telomerase activityen_ZA
dc.typeThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Pavan Baichan MSc Dissertation Final Submission.pdf
Size:
1.81 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
ETD Collection