Hawsawi, Y, El-Gendy, R, Twelves, C et al. (2 more authors) (2013) Insulin-like growth factor - Oestradiol crosstalk and mammary gland tumourigenesis. BBA - Reviews on Cancer, 1836 (2). 345 - 353. ISSN 0304-419X
Abstract
Development and differentiation of the mammary gland are dependent on the appropriate temporal expression of both systemically acting hormones and locally produced growth factors. A large body of evidence suggests that molecular crosstalk between these hormonal and growth factor axes is crucial for appropriate cell and tissue function. Two of the most important trophic factors involved in this process are the oestrogen (E) and insulin-like growth factor (IGF) molecular axes. The reciprocal crosstalk that exists between these pathways occurs at transcriptional/post-transcriptional and translational/post-translational levels regulate the expression and activity of genes involved in this process. In a clinical context an important consequence of such crosstalk in the mammary gland is the role which it may play in the aetiology, maintenance and development of breast tumours. Although oestradiol (E2) acting through oestrogen receptors α and β (ERα/β) is important for normal mammary gland function it can also provide a mitogenic drive to ER+ breast tumours. Therefore over several years anti-oestrogen therapeutic regimens in the form of selective oestrogen receptor modulators (SERMs - e.g. tamoxifen), aromatase inhibitors (AI e.g. anastrozole) or selective oestrogen receptor down regulators (SERDs - e.g. fulvestrant) have been used in an adjuvant setting to control tumour growth. Although initial response is usually encouraging, large cohorts of patients eventually develop resistance to these treatments leading to tumour recurrence and poor prognosis. There are potentially many routes by which breast cancer (BC) cells could escape anti-oestrogen based therapeutic strategies and one of the most studied is the possible growth factor mediated activation of ER(s). Because of this, growth factor modulation of ER activity has been an intensively studied route of molecular crosstalk in the mammary gland. The insulin-like growth factors (IGF-1 and -2) are amongst the most potent mitogens for mammary epithelial cells and there is accumulating evidence that they interact with the E2 axis to regulate mitogenesis, apoptosis, adhesion, migration and differentiation of mammary epithelial cells. Such interactions are bi-directional and E2 has been shown to regulate the expression and activity of IGF axis genes with the general effect of sensitising breast epithelial cells to the actions of IGFs and insulin. In this short review we discuss the evidence for the involvement of crosstalk between the insulin-like growth factor (IGF) and oestrogen axes in the mammary gland and comment on the relevance of such studies in the aetiology and treatment of BC.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 Elsevier B.V. NOTICE: this is the author’s version of a work that was accepted for publication in BBA - Reviews on Cancer. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in BBA - Reviews on Cancer , 1836(2),(2013) DOI:10.1016/j.bbcan.2013.10.005 |
Keywords: | Insulin-like growth factor; Oestradiol; Breast cancer; Endocrine resistance |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Oct 2014 09:46 |
Last Modified: | 17 Jan 2018 12:04 |
Published Version: | http://dx.doi.org/10.1016/j.bbcan.2013.10.005 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.bbcan.2013.10.005 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:80781 |