Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines

Breast cancer is the most common cancer-affecting women with the most common subtype is HER2 positive breast cancer. Patients with HER2 positive breast cancer are treated with Herceptin, a monoclonal anti-HER2 antibody that is proven to improve survival. Unfortunately, the incidence of primary or ac...

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Main Author: Ali, Nursyazana Aqilah
Format: Thesis
Language:English
Published: 2021
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Online Access:http://eprints.usm.my/57782/1/NURSYAZANA%20AQILAH%20BINTI%20ALI-FINAL%20THESIS%20P-UM000817%28R%29-24%20pages.pdf
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spelling my-usm-ep.577822023-04-11T02:45:46Z Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines 2021-01 Ali, Nursyazana Aqilah R Medicine RC254-282 Neoplasms. Tumors. Oncology (including Cancer) Breast cancer is the most common cancer-affecting women with the most common subtype is HER2 positive breast cancer. Patients with HER2 positive breast cancer are treated with Herceptin, a monoclonal anti-HER2 antibody that is proven to improve survival. Unfortunately, the incidence of primary or acquired resistance to Herceptin remains a challenge for an effective treatment. The overexpressions of HER family receptors such as HER1, HER3 and HER4 are one of the mechanisms of Herceptin resistance. Among the HER family receptors, the role of HER4 in breast cancer is uncertain where some reports suggest a tumour suppressive function while others suggest an oncogenic function. The conflicting role of HER4 is due to the presence of different isoforms and nuclear translocation of HER4. In this study, we investigated the expression of HER4 isoforms and its localisation in HER2-negative cell lines, MCF-7 and MDA-MB 231. The expression of HER4 isoforms (CYT-1, CYT-2, JM-a and JM-b) was determined by qRT-PCR, while nuclear and cytoplasmic localisation of HER4 was determined by western blot. There is a variability of HER4 isoforms expressions in between the MDA-MB-231 (HER2-/ER+/PR+) and MCF-7 (HER2-/ER+/PR+). Nuclear and cytoplasmic HER4 were highly expressed in MCF-7 cells than MDA-MB 231. High expressions of HER4 isoforms and HER4 localisations in MCF-7 that have positive ER expression may suggest a possible association of HER4 and ER in mediating the mechanism of anti- HER2 resistance. In future, understanding on the role of HER4-ER interaction in anti-HER2 resistance is warranted. 2021-01 Thesis http://eprints.usm.my/57782/ http://eprints.usm.my/57782/1/NURSYAZANA%20AQILAH%20BINTI%20ALI-FINAL%20THESIS%20P-UM000817%28R%29-24%20pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution Universiti Sains Malaysia
collection USM Institutional Repository
language English
topic R Medicine
R Medicine
spellingShingle R Medicine
R Medicine
Ali, Nursyazana Aqilah
Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines
description Breast cancer is the most common cancer-affecting women with the most common subtype is HER2 positive breast cancer. Patients with HER2 positive breast cancer are treated with Herceptin, a monoclonal anti-HER2 antibody that is proven to improve survival. Unfortunately, the incidence of primary or acquired resistance to Herceptin remains a challenge for an effective treatment. The overexpressions of HER family receptors such as HER1, HER3 and HER4 are one of the mechanisms of Herceptin resistance. Among the HER family receptors, the role of HER4 in breast cancer is uncertain where some reports suggest a tumour suppressive function while others suggest an oncogenic function. The conflicting role of HER4 is due to the presence of different isoforms and nuclear translocation of HER4. In this study, we investigated the expression of HER4 isoforms and its localisation in HER2-negative cell lines, MCF-7 and MDA-MB 231. The expression of HER4 isoforms (CYT-1, CYT-2, JM-a and JM-b) was determined by qRT-PCR, while nuclear and cytoplasmic localisation of HER4 was determined by western blot. There is a variability of HER4 isoforms expressions in between the MDA-MB-231 (HER2-/ER+/PR+) and MCF-7 (HER2-/ER+/PR+). Nuclear and cytoplasmic HER4 were highly expressed in MCF-7 cells than MDA-MB 231. High expressions of HER4 isoforms and HER4 localisations in MCF-7 that have positive ER expression may suggest a possible association of HER4 and ER in mediating the mechanism of anti- HER2 resistance. In future, understanding on the role of HER4-ER interaction in anti-HER2 resistance is warranted.
format Thesis
qualification_level Master's degree
author Ali, Nursyazana Aqilah
author_facet Ali, Nursyazana Aqilah
author_sort Ali, Nursyazana Aqilah
title Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines
title_short Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines
title_full Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines
title_fullStr Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines
title_full_unstemmed Expression of HER4 isoforms and HER4 localisation in HER2 negative breast cancer cell lines
title_sort expression of her4 isoforms and her4 localisation in her2 negative breast cancer cell lines
granting_institution Universiti Sains Malaysia
granting_department Pusat Pengajian Sains Perubatan
publishDate 2021
url http://eprints.usm.my/57782/1/NURSYAZANA%20AQILAH%20BINTI%20ALI-FINAL%20THESIS%20P-UM000817%28R%29-24%20pages.pdf
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