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The Role of Activin in Mammary Gland Development and Oncogenesis

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

TGFβ contributes to mammary gland development and has paradoxical roles in breast cancer because it has both tumor suppressor and tumor promoter activity. Another member of the TGFβ superfamily, activin, also has roles in the developing mammary gland, but these functions, and the role of activin in breast cancer, are not well characterized. TGFβ and activin share the same intracellular signaling pathways, but divergence in their signaling pathways are suggested. The purpose of this review is to compare the spatial and temporal expression of TGFβ and activin during mammary gland development, with consideration given to their functions during each developmental period. We also review the contributions of TGFβ and activin to breast cancer resistance and susceptibility. Finally, we consider the systemic contributions of activin in regulating obesity and diabetes; and the impact this regulation has on breast cancer. Elevated levels of activin in serum during pregnancy and its influence on pregnancy associated breast cancer are also considered. We conclude that evidence demonstrates that activin has tumor suppressing potential, without definitive indication of tumor promoting activity in the mammary gland, making it a good target for development of therapeutics.

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Abbreviations

TGFβ:

Transforming Growth Factor Beta

EMT:

Epithelial and Mesenchymal Transition

Alk:

Activin Receptor-Like Kinase

BMP:

Bone Morphogenic Protein

LAP:

Latency-Associated Peptide

FST:

Follistatin

FSTL3:

Follistatin-Like 3

BAMBI:

Follistatin-Related Gene, FLRG, BMP and Activin Membrane Bound Inhibitor

ARIP:

Activin Receptor-Interacting Proteins

TEB:

Terminal End Bud

ECM:

Extracellular Matrix

WT:

Wild-type

ER:

estrogen receptor

AIF:

Apoptosis-Inducing Factor

TERT:

Telomerase Reverse Transcriptase

HMEC:

Human Mammary Epithelial Cells

PABC:

Pregnancy Associated Breast Cancer

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Financial and Material Support

The research was supported by funds from Avon Foundation (DJJ), National Institutes of Health (R0-1-CA105452; R01-ES015739, DJJ; R01-DK075058, AS; R21-HD062859, AS) and Department of Defense (W81XWH-10-1-0637, DJJ, KAD)

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Authors and Affiliations

  1. Department of Veterinary and Animal Science, University of Massachusetts-Amherst, Amherst, MA, USA

    Karen A. Dunphy, Mary J. Hagen & D. Joseph Jerry

  2. Pioneer Valley Life Sciences Institute, 3601 Main Street, Springfield, MA, 01107, USA

    Alan L. Schneyer & D. Joseph Jerry

Authors
  1. Karen A. Dunphy
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  2. Alan L. Schneyer
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  3. Mary J. Hagen
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  4. D. Joseph Jerry
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Correspondence to Karen A. Dunphy or D. Joseph Jerry.

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Dunphy, K.A., Schneyer, A.L., Hagen, M.J. et al. The Role of Activin in Mammary Gland Development and Oncogenesis. J Mammary Gland Biol Neoplasia 16, 117–126 (2011). https://doi.org/10.1007/s10911-011-9214-4

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  • DOI: https://doi.org/10.1007/s10911-011-9214-4

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