Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium

Keiko Miyoshi, Jonathan M. Shillingford, Gilbert H. Smith, Sandra L. Grimm, Kay-Uwe Wagner, Takami Oka, Jeffrey M. Rosen, Gertraud W. Robinson, Lothar Hennighausen

Research output: Contribution to journalArticle

218 Citations (Scopus)

Abstract

Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrlR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell-cell contacts in PrlR-and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrlR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrlR- and Stat5-null mice. These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy.

Original languageEnglish (US)
Pages (from-to)531-542
Number of pages12
JournalJournal of Cell Biology
Volume155
Issue number3
StatePublished - Oct 29 2001

Fingerprint

STAT5 Transcription Factor
Prolactin Receptors
Breast
Epithelium
Pregnancy
Sodium-Potassium-Chloride Symporters
Tight Junctions
Milk Proteins
Gap Junctions
Organelles
Prolactin
Electron Microscopy
Gene Expression

Keywords

  • Cell specification
  • Epithelia
  • Mammary gland
  • Prolactin receptor
  • Stat5

ASJC Scopus subject areas

  • Cell Biology

Cite this

Miyoshi, K., Shillingford, J. M., Smith, G. H., Grimm, S. L., Wagner, K-U., Oka, T., ... Hennighausen, L. (2001). Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. Journal of Cell Biology, 155(3), 531-542.

Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. / Miyoshi, Keiko; Shillingford, Jonathan M.; Smith, Gilbert H.; Grimm, Sandra L.; Wagner, Kay-Uwe; Oka, Takami; Rosen, Jeffrey M.; Robinson, Gertraud W.; Hennighausen, Lothar.

In: Journal of Cell Biology, Vol. 155, No. 3, 29.10.2001, p. 531-542.

Research output: Contribution to journalArticle

Miyoshi, K, Shillingford, JM, Smith, GH, Grimm, SL, Wagner, K-U, Oka, T, Rosen, JM, Robinson, GW & Hennighausen, L 2001, 'Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium', Journal of Cell Biology, vol. 155, no. 3, pp. 531-542.
Miyoshi, Keiko ; Shillingford, Jonathan M. ; Smith, Gilbert H. ; Grimm, Sandra L. ; Wagner, Kay-Uwe ; Oka, Takami ; Rosen, Jeffrey M. ; Robinson, Gertraud W. ; Hennighausen, Lothar. / Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. In: Journal of Cell Biology. 2001 ; Vol. 155, No. 3. pp. 531-542.
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