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HER2-PI9 and HER2-I12: two novel and functionally active splice variants of the oncogene HER2 in breast cancer

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.

Publication metadata

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


DOI: 10.1007/s00432-021-03689-1


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