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Transforming growth factor-beta regulator SnoN modulates mammary gland branching morphogenesis, postlactational

Nadine S Jahchan1, Young-Hyun You, William J Muller

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.

Cancer Research
|May 13, 2010
PubMed

Insights

SnoN, a transforming growth factor-beta (TGF-beta) regulator, promotes mammary epithelial cell proliferation and accelerates involution. Elevated SnoN cooperates with oncogenes to drive aggressive mammary tumors and metastasis in mice.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Developmental Biology

Background:

  • SnoN is a key negative regulator of TGF-beta signaling.
  • Its role in normal mammalian epithelial cells, particularly in mammary development, remains undefined.
  • Previous studies reported both pro-oncogenic and anti-oncogenic activities of SnoN.

Purpose of the Study:

  • To investigate the function of SnoN in normal mouse mammary gland epithelial cells.
  • To determine the effects of elevated SnoN levels on mammary gland development and tumorigenesis.
  • To provide in vivo evidence for SnoN's role in mammalian cancer progression.

Main Methods:

  • Generated transgenic mice expressing a SnoN fragment under the MMTV promoter.
  • Analyzed mammary gland morphology, proliferation, and involution dynamics.
  • Assessed cooperation between elevated SnoN and polyoma middle T antigen in tumorigenesis.

Main Results:

  • SnoN elevation increased mammary side-branching and lobular-alveolar proliferation in virgin mice.
  • Elevated SnoN accelerated involution in postlactation mammary glands.
  • SnoN alone did not induce mammary tumors, but cooperated with polyoma middle T antigen to accelerate aggressive adenocarcinoma formation and pulmonary metastasis.

Conclusions:

  • SnoN plays critical roles in regulating mammary epithelial cell proliferation and gland involution.
  • This study provides the first in vivo evidence of a pro-oncogenic role for SnoN in mammalian mammary tumorigenesis.
  • SnoN acts as a cooperating oncogene in mammary cancer development and metastasis.

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