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The kisspeptin signalling pathway and its role in breast cancer biology
Thesis (PhD (Human Physiology))--University of Pretoria, 2022.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2022
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| _version_ | 1867613576711110656 |
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| access_status_str | Open Access |
| author2 | Van den Bout, Iman |
| author_browse | Van den Bout, Iman |
| author_facet | Van den Bout, Iman |
| collection | Thesis |
| dc_rights_str_mv | © 2022 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD (Human Physiology))--University of Pretoria, 2022. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/86775 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:38:21.029Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/86775 The kisspeptin signalling pathway and its role in breast cancer biology Van den Bout, Iman feliciaazubuike@gmail.com Newton, Claire Azubuike, Udochi Felicia Breast cancer Cancer biology Cell signalling Cell migration Calcium Kisspeptin UCTD Thesis (PhD (Human Physiology))--University of Pretoria, 2022. Kisspeptin is a neuropeptide that was first identified as a metastasis suppressor in human melanoma. It is the endogenous ligand for the G protein-coupled receptor, Kisspeptin 1 receptor (KISS1R). In addition to melanoma, Kisspeptin has since been shown to inhibit metastasis in pancreatic, lung, bladder, and ovarian cancers. However, in breast cancer, some data suggest that it may have a pro-metastatic effect, at least in oestrogen receptor-negative (ER-) breast cancers. However, the exact mechanisms of how this is achieved, and if this effect is universal for all ER- breast cancers, remains unclear. This study aimed to shed light on the ability of Kisspeptin to induce cell signalling related to metastasis in two triple-negative breast cancer (TNBC) cell lines. The non-metastatic BT-20 and the metastatic MDA-MB-231 TNBC cell lines were selected as they have very different migratory and metastatic characteristics. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to assess KISS1R mRNA expression while Western blot analysis was used to investigate extracellular signal-regulated kinase 1 and 2 (ERK1/2) and protein kinase B (Akt/PKB) phosphorylation, and β-arrestin1/2 expression. Calcium signalling was measured using Fluo-3 AM, cell proliferation was measured using resazurin, and cell migration was assessed using an Oris™ migration assay. It was found that both cell lines express endogenous KISS1R mRNA. However, ERK1/2 and Akt phosphorylation and calcium mobilisation occurred in the BT-20 cell line after Kisspeptin-10 (KP-10) stimulation. ERK1/2 phosphorylation occurred late, in a β-arrestin-dependent manner. In contrast, only Akt phosphorylation and calcium mobilisation occurred in MDA-MB-231 cells after stimulation with KP-10. KP-10 increased migration in a calcium-dependent manner in the MDA-MB-231 cell line. KP-10 did not increase cell proliferation in either cell line. These data suggest that in these two related cell lines different signalling and physiological outcomes are initiated after KP-10 stimulation. This means that beyond the presence of Kisspeptin and KISS1R or Kisspeptin signalling, it is likely that other specific internal cellular signalling components also need to be present for Kisspeptin to act in a pro-metastatic manner in ER- breast cancer. The data also suggest that Kisspeptin and KISS1R may not play a pro-metastatic role in all ER- breast cancers. NRF Physiology PhD (Human Physiology) Unrestricted 2022-08-12T06:20:37Z 2022-08-12T06:20:37Z 2022-09-09 2022 Thesis * S2022 https://repository.up.ac.za/handle/2263/86775 DOI: 10.25403/UPresearchdata.20405847 https://doi.org/10.25403/UPresearchdata.20405847 en © 2022 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | Breast cancer Cancer biology Cell signalling Cell migration Calcium Kisspeptin UCTD The kisspeptin signalling pathway and its role in breast cancer biology |
| title | The kisspeptin signalling pathway and its role in breast cancer biology |
| title_full | The kisspeptin signalling pathway and its role in breast cancer biology |
| title_fullStr | The kisspeptin signalling pathway and its role in breast cancer biology |
| title_full_unstemmed | The kisspeptin signalling pathway and its role in breast cancer biology |
| title_short | The kisspeptin signalling pathway and its role in breast cancer biology |
| title_sort | kisspeptin signalling pathway and its role in breast cancer biology |
| topic | Breast cancer Cancer biology Cell signalling Cell migration Calcium Kisspeptin UCTD |
| url | https://repository.up.ac.za/handle/2263/86775 https://doi.org/10.25403/UPresearchdata.20405847 |