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Inhibition of ductal morphogenesis in the mammary gland of WAP-fgf4 transgenic mice

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Abstract

We previously demonstrated that expression of human FGF4 in the epithelial compartment of murine mammary glands caused hyperplasia during lactation and a dramatic delay in gland involution due to inhibition of cellular apoptosis. We now analyse the effects of transgene expression during development of the organ. Expression of WAP-Fgf4 initiate with the onset of sexual hormones (4 weeks of age), and defects in morphogenesis of the organ were already apparent at 5 weeks of age and persisted throughout all stages of post-natal development. These defects involved ductal development, but not lobuloalveolar morphogenesis, and were due to a decrease in the level of apoptosis within the terminal end buds. We also show that regulation of apoptosis by FGF4 in the mammary gland, both during development and involution, could occur via inhibition of Bcl2 expression. Overall our data demonstrate that FGF4 is a regulator of mammary epithelial cells apoptosis during all stages in which programmed cell death is an important mechanism of development, namely morphogenesis and involution. We also suggest that this growth factor could act by interfering with the Bcl2 pathway.

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Abbreviations

FGF :

Fibroblast growth factors

FGFr :

Fibroblast growth factors and their receptors

MMPs :

Remodelling by metalloproteases

PB :

Phosphate-buffered saline

RT :

Room temperature

TEB :

Terminal end buds

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Acknowledgments

We are grateful to Dr. Nicoletta Ferrari for her help with the PCR, and to Luca Boni for his technical assistance. This work has been supported in part by COFIN MURST to O.B.

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Authors and Affiliations

  1. Unita Transgenici, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 , Genoa, Italy

    Simonetta Astigiano

  2. Dipartimento di Oncologia, Biologia e Genetica dell'Università di Genova, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 , Genoa, Italy

    Patrizia Damonte & Ottavia Barbieri

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  1. Simonetta Astigiano
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  2. Patrizia Damonte
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  3. Ottavia Barbieri
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Correspondence to Simonetta Astigiano.

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Astigiano, S., Damonte, P. & Barbieri, O. Inhibition of ductal morphogenesis in the mammary gland of WAP-fgf4 transgenic mice. Anat Embryol 206, 471–478 (2003). https://doi.org/10.1007/s00429-003-0317-6

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