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Breast Cancer Research and Treatment

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01-02-2020 | Breast Cancer | Preclinical study

Amphiregulin deletion strongly attenuates the development of estrogen receptor-positive tumors in p53 mutant mice

Authors: David R. Meier, Megan A. Girtman, Kristopher A. Lofgren, Paraic A. Kenny

Published in: Breast Cancer Research and Treatment | Issue 3/2020

Abstract

Purpose

The epidermal growth factor receptor ligand, Amphiregulin, is a transcriptional target of estrogen receptor alpha and is required for pubertal mammary gland development. Previous studies using immortalized human breast cancer cell line xenografts have suggested that Amphiregulin may be an important effector of estrogen receptor alpha during breast cancer development, at least in immune-compromised animals. Here, we evaluate the requirement for Amphiregulin in an immune-competent mouse model which is prone to developing estrogen receptor-positive tumors.

Methods

We have intercrossed mice with mammary-specific mutation of p53 with mice deficient in Amphiregulin in order to assess the requirement for Amphiregulin in the initiation and progression of both estrogen receptor-positive and estrogen receptor-negative mammary tumors.

Results

Deletion of Amphiregulin significantly delayed the onset of palpable mammary tumors and also strongly reduced the proportion of estrogen receptor alpha-positive tumors formed. Upon necropsy, no substantial differences in the prevalence of non-palpable lesions were observed between cohorts, suggesting that the importance of Amphiregulin in mammary tumorigenesis is limited to the post-initiation phase.

Conclusions

This study underlines the importance of the EGFR ligand, Amphiregulin, as a key mediator of estrogen receptor action in breast cancer.

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Title: Amphiregulin deletion strongly attenuates the development of estrogen receptor-positive tumors in p53 mutant mice
Authors: David R. Meier
Megan A. Girtman
Kristopher A. Lofgren
Paraic A. Kenny
Publication date: 01-02-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Estrogens
Published in: Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05507-2

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Abstract

Purpose

Methods

Results

Conclusions

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