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Journal of Mammary Gland Biology and Neoplasia

Published in:

01-06-2008

The Neuregulin Family of Genes and their Multiple Splice Variants in Breast Cancer

Authors: Nandini V. L. Hayes, William J. Gullick

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 2/2008

Abstract

The neuregulin family consists of four genes, NRG1–4 which can each encode products containing a domain related to the epidermal growth factor family of ligands. Each gene is subject to complex control of transcription and to splicing of their mRNA product to give many variant proteins. These do not contain secretory sequences but some, through their transmembrane sequence, are routed via the Golgi where they are glycosylated, to the cell surface. Here they may be released by regulated proteolysis to act as soluble proteins which can interact and activate members of the EGF receptor family of receptor tyrosine kinases. Other splice variants do not encode transmembrane sequences and these are found either in the cytoplasm or, if they encode a nuclear localisation sequence, in distinct compartments in the nucleoplasm. It has been shown that the variants containing a full EGF domain can act as receptor agonists but the function of the cytoplasmic and nuclear products is unknown as yet. All four neuregulin genes are expressed and play an important role in mammary gland development. They are also expressed at elevated levels in some cases of ductal carcinoma in situ of the breast and breast cancer. They seem to be active in this setting and their presence may affect the efficacy of treatment with endocrine agents or with signal transduction inhibitors directed at the EGF receptor family members. Much remains to be learned however of their normal function and their influence on breast cancer development, progression and response to therapy.

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Title: The Neuregulin Family of Genes and their Multiple Splice Variants in Breast Cancer
Authors: Nandini V. L. Hayes
William J. Gullick
Publication date: 01-06-2008
Publisher: Springer US
Published in: Journal of Mammary Gland Biology and Neoplasia / Issue 2/2008
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-008-9078-4

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Other articles of this Issue 2/2008

HER4 Intracellular Domain (4ICD) Activity in the Developing Mammary Gland and Breast Cancer

The Epidermal Growth Factor Family of Ligands and Receptors Grows and Grows

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