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Lookup NU author(s): Vic Hart, Marco Silipo, Swapna Satam, Dr Hannah Gautrey, Emeritus Professor John Kirby, Professor Alison Tyson-Capper
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s). In this study, two novel alternative splice variants of HER2, named HER2-PI9 and HER2-I12, were identified in breast cancer cell lines and breast tumour tissues. Whilst HER2-P19 arises from the inclusion of an 117 bp cassette-exon of intron 9 of HER2, HER2-I12 results from intron 12 inclusion. In silico analyses were performed to predict the amino acid sequences of these two HER2 novel variants. To confirm their protein expression, plasmid vectors were generated and transfected into the HER2 negative breast cancer cell line, MCF-7. Additionally, their functional properties in oncogenic signalling were confirmed. Expression of HER2-PI9 and HER2-I12 was successful and matched the in silico predictions. Importantly, these splice variants can modulate the phosphorylation levels of extracellular signal-related kinase 1/2 (ERK1/2) and Akt/protein kinase B (Akt) signalling in MCF-7 breast cancer cells. Enhanced cellular proliferation, migration and invasion were observed in the case of the HER2-I12 expressing model. In human tissues and breast carcinoma tumours both variants were present. This study reveals two novel splice variants of HER2. Additionally, the potential biological activity for HER2-PI9 and HER2-I12 in breast cancer cells is also reported.
Author(s): Hart V, Silipo M, Satam S, Gautrey H, Kirby J, Tyson-Capper A
Publication type: Article
Publication status: Published
Journal: Journal of Cancer Research and Clinical Oncology
Year: 2021
Volume: 147
Pages: 2893-2912
Print publication date: 01/10/2021
Online publication date: 16/06/2021
Acceptance date: 05/06/2021
Date deposited: 28/06/2021
ISSN (print): 0171-5216
ISSN (electronic): 1432-1335
Publisher: Springer Science and Business Media Deutschland GmbH
URL: https://doi.org/10.1007/s00432-021-03689-1
DOI: 10.1007/s00432-021-03689-1
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