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Oncogenic signaling pathways activated in DMBA-induced mouse mammary tumors

Nicolas Currier1, Sandra E Solomon, Elizabeth G Demicco

  • 1Boston University School of Medicine, Department of Medicine, Boston, MA, USA.

Toxicologic Pathology
|November 3, 2005
PubMed

Insights

Environmental carcinogens like DMBA can trigger long-term changes in growth pathways, leading to mammary tumors. This study reveals how DMBA activates oncogenic signaling pathways in mice, contributing to breast cancer development.

Area of Science:

  • Oncology
  • Environmental Health
  • Molecular Biology

Background:

  • Most human breast cancers are sporadic, influenced by environmental factors rather than inherited genes.
  • The impact of environmental carcinogens on cellular growth control pathways remains largely unknown.
  • Polycyclic aromatic hydrocarbons (PAHs) are environmental carcinogens with poorly understood mechanisms in breast cancer.

Purpose of the Study:

  • To investigate oncogenic signaling pathways activated by the PAH 7,12-dimethylbenz[a]anthracene (DMBA) in mouse mammary tumors.
  • To understand the long-term effects of environmental carcinogen exposure on cell growth and apoptosis.
  • To identify specific molecular pathways involved in DMBA-induced mammary tumorigenesis.

Main Methods:

  • Female FVB mice were administered weekly doses of DMBA via gavage.
  • Mammary tumor development and incidence were monitored over time.
  • Expression levels of key proteins (Aryl hydrocarbon receptor (AhR), c-myc, cyclin D1, retinoblastoma (Rb)) and signaling pathways (Wnt, NF-kappa B, Pin-1) were assessed in tumors.

Main Results:

  • DMBA treatment led to a high incidence of mammary tumors in mice.
  • DMBA-induced tumors showed elevated expression of AhR, c-myc, cyclin D1, and hyperphosphorylated Rb.
  • Up-regulation of Wnt signaling, NF-kappa B pathway, and Pin-1 was frequently observed in tumors compared to normal mammary glands.

Conclusions:

  • Environmental carcinogens like DMBA can induce sustained alterations in critical growth and anti-apoptotic pathways.
  • These pathway alterations contribute to the development of mammary tumors.
  • The study highlights the role of specific signaling pathways in carcinogen-induced breast cancer.

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