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First published online December 15, 2003
doi: 10.1242/10.1242/jcs.00855

Journal of Cell Science 117, 271-280 (2004)
Published by The Company of Biologists 2004
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Research Article

A role for the cytoskeleton in prolactin-dependent mammary epithelial cell differentiation

Ghada S. Zoubiane1, Anthony Valentijn1, Emma T. Lowe1, Nasreen Akhtar1, Steve Bagley1,2, Andrew P. Gilmore1 and Charles H. Streuli1,*

1 School of Biological Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK
2 CRC Structural Cell Biology Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 9BX, UK

* Author for correspondence (e-mail: cstreuli{at}man.ac.uk)

Accepted 5 September 2003

The function of exocrine glands depends on signals within the extracellular environment. In the mammary gland, integrin-mediated adhesion to the extracellular matrix protein laminin co-operates with soluble factors such as prolactin to regulate tissue-specific gene expression. The mechanism of matrix and prolactin crosstalk and the activation of downstream signals are not fully understood. Because integrins organize the cytoskeleton, we analysed the contribution of the cytoskeleton to prolactin receptor activation and the resultant stimulation of milk protein gene expression. We show that the proximal signalling events initiated by prolactin (i.e. tyrosine phosphorylation of receptor and the associated kinase Jak2) do not depend on an intact actin cytoskeleton. However, actin networks and microtubules are both necessary for continued mammary cell differentiation, because cytoskeletal integrity is required to transduce the signals between prolactin receptor and Stat5, a transcription factor necessary for milk protein gene transcription. The two different cytoskeletal scaffolds regulate prolactin signalling through separate mechanisms that are specific to cellular differentiation but do not affect the general profile of protein synthesis.

Key words: Cytochalasin D, Colchicine, Cytoskeleton, Microtubules, Prolactin, Mammary epithelial differentiation


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