Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1

Bradley A. Creamer, Kazuhito Sakamoto, Jeffrey W. Schmidt, Aleata A. Triplett, Richard Moriggl, Kay Uwe Wagner

Research output: Contribution to journalArticle

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Abstract

The signal transducer and activator of transcription 5 (Stat5) plays a pivotal role in the proliferation, secretory differentiation, and survival of mammary epithelial cells. However, there is little information about Stat5 target genes that facilitate these biological processes. We provide here experimental evidence that the prolactin-mediated phosphorylation of Stat5 regulates the transcriptional activation of the Akt1 gene. Stat5 binds to consensus sequences within the Akt1 locus in a growth factor-dependent manner to initiate transcription of a unique Akt1 mRNA from a distinct promoter, which is only active in the mammary gland. Elevating the levels of active Akt1 restores the expression of cyclin D1 and proliferation of Jak2-deficient mammary epithelial cells, which provides evidence that Akt1 acts downstream of Jak/Stat signaling. The ligand-inducible expression of Stat5 in transgenic females mediates a sustained upregulation of Akt1 in mammary epithelial cells during the onset of postlactational involution. Stat5-expressing mammary glands exhibit a delay in involution despite induction of proapoptotic signaling events. Collectively, the results of the present study elucidate an underlying mechanism by which active Stat5 mediates evasion from apoptosis and self-sufficiency in growth signals.

Original languageEnglish (US)
Pages (from-to)2957-2970
Number of pages14
JournalMolecular and cellular biology
Volume30
Issue number12
DOIs
StatePublished - Jun 1 2010

Fingerprint

STAT5 Transcription Factor
Transcriptional Activation
Breast
Epithelial Cells
Human Mammary Glands
Biological Phenomena
Cyclin D1
Consensus Sequence
Prolactin
Genes
Intercellular Signaling Peptides and Proteins
Up-Regulation
Phosphorylation
Apoptosis
Ligands
Messenger RNA
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Creamer, B. A., Sakamoto, K., Schmidt, J. W., Triplett, A. A., Moriggl, R., & Wagner, K. U. (2010). Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1. Molecular and cellular biology, 30(12), 2957-2970. https://doi.org/10.1128/MCB.00851-09

Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1. / Creamer, Bradley A.; Sakamoto, Kazuhito; Schmidt, Jeffrey W.; Triplett, Aleata A.; Moriggl, Richard; Wagner, Kay Uwe.

In: Molecular and cellular biology, Vol. 30, No. 12, 01.06.2010, p. 2957-2970.

Research output: Contribution to journalArticle

Creamer, Bradley A. ; Sakamoto, Kazuhito ; Schmidt, Jeffrey W. ; Triplett, Aleata A. ; Moriggl, Richard ; Wagner, Kay Uwe. / Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1. In: Molecular and cellular biology. 2010 ; Vol. 30, No. 12. pp. 2957-2970.
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