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Evaluation of Mammary Gland Development and Function in Mouse Models
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Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

Jane Q Chen1, Hidetoshi Mori1, Robert D Cardiff1

  • 1Center for Comparative Medicine, University of California, Davis, California, United States of America.

Plos One
|June 16, 2015
PubMed
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Stat1-null mice develop estrogen-receptor-positive mammary tumors due to impaired mammary gland development. Hormonal factors and mammary stroma cytokines influence tumor growth, suggesting STAT1

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Area of Science:

  • Reproductive biology
  • Cancer biology
  • Immunology

Background:

  • STAT1 (Signal transducer and activator of transcription 1) plays a role in immune responses and cell growth.
  • STAT1-null mice exhibit unique phenotypes, including mammary tumor development.
  • Mammary gland (MG) development is a complex process regulated by hormones and local microenvironment.

Purpose of the Study:

  • To investigate the role of STAT1 in mammary gland development and tumorigenesis.
  • To identify factors contributing to the altered MG development and tumor growth in STAT1-null mice.
  • To explore the potential of hormonal milieu and mammary stroma in modulating MG growth and tumor progression.

Main Methods:

  • Phenotypic analysis of mammary glands in 129:Stat1-null mice.
  • Mammary fat pad (MFP) transplantation experiments.
  • In vitro studies using conditioned media from epithelial cells and MFP.
  • Microarray analysis and multiplexed cytokine assays.
  • Tumorigenesis studies using transplanted tumors and isolated cells.

Main Results:

  • 129:Stat1-null mice exhibit abnormal MG development, including defective branching and ductal elongation.
  • The MFP of 129:Stat1-null mice fails to support normal epithelial growth.
  • Elevated progesterone and prolactin partially reverse MG abnormalities.
  • STAT1-null MG shows reduced levels of critical growth factors and cytokines.
  • Tumors derived from STAT1-null cells grow slower in STAT1-null MG compared to wild-type MG.

Conclusions:

  • STAT1 is crucial for normal mammary gland development and maintaining a tumor-suppressive microenvironment.
  • Mammary gland development and neoplastic growth in STAT1-null mice are significantly influenced by hormonal milieu and mammary stroma-derived factors.
  • Cytokines and growth factors within the MG microenvironment are critical regulators of both normal and neoplastic epithelial cell behavior.