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Deregulation of Stat5 expression and activation causes mammary tumors in transgenic mice

Elena Iavnilovitch1, Robert D Cardiff, Bernd Groner

  • 1Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet-Dagan, Israel.

International Journal of Cancer
|September 24, 2004
PubMed

Insights

Signal transducers and activators of transcription 5 (Stat5) variants promote mammary tumors in mice. Different Stat5 forms influence tumor type and molecular markers, revealing multiple oncogenic pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Signal transducers and activators of transcription (Stat) proteins regulate cell growth and survival.
  • Stat family members are implicated in various cancers, including tumorigenesis.
  • The specific role of Stat5 in mammary gland cancer requires further investigation.

Purpose of the Study:

  • To investigate the role of Signal transducers and activators of transcription 5 (Stat5) in mammary tumorigenesis.
  • To analyze the impact of different Stat5 variants on tumor development and characteristics.
  • To explore the molecular mechanisms underlying Stat5-driven mammary tumors.

Main Methods:

  • Generation of transgenic mice with mammary-gland-specific expression of wild-type, constitutively active, and dominant-negative Stat5 variants.
  • Analysis of tumor incidence, latency, and histological phenotypes.
  • Assessment of molecular markers including translation initiation factor 4E (eIF4E), cyclin D1, activated Stat3, and estrogen receptor alpha (ERalpha).

Main Results:

  • Mammary-directed expression of Stat5 variants led to mammary tumors with up to 22% incidence and 8-12 month latency.
  • Undifferentiated carcinomas were associated with carboxyl-terminally truncated Stat5.
  • Papillary and micropapillary adenocarcinomas were linked to native and constitutively active Stat5, with altered eIF4E, cyclin D1, Stat3, and ERalpha expression.

Conclusions:

  • Both transactivating and dominant-negative Stat5 forms can contribute to oncogenesis through distinct mechanisms.
  • Stat5 plays a significant role in mammary tumorigenesis.
  • The transactivation function of Stat5 influences the differentiation state of mammary tumors.

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