PPARδ is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer

Mallika Ghosh, Youxi Ai, Kirsi Narko, Zhenglong Wang, Jeffrey M. Peters, Timothy Hla

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Cyclooxygenase-2 (COX-2), overexpressed in inflammatory conditions and cancer, regulates angiogenesis and tumorigenesis via the production of biologically active prostanoids. Previously, we showed that COX-2 over-expression in the mammary gland of transgenic mice induces an angiogenic switch and transforms the mammary epithelium into invasive mammary carcinoma. Since COX-2-derived prostanoids can activate the nuclear receptor PPARδ, we crossed Pparδ-/- mice with COX-2 transgenic mice in the FVB/N background. PPARδ was expressed constitutively in the mammary gland of virgin, pregnant and lactating mice. Mammary hyperplasia and tumorigenesis in the COX-2 transgenic mice was markedly reduced in the Pparδ-/- mice compared to their wild type counterparts. Analysis of the mammary tissues indicated that immunoreactive Ki-67, cyclin D1 and phosphorylated histone 3 (Phospho H3) were reduced in Pparδ-/- mice, suggesting that PPARδ activation regulates cell proliferation in the mammary gland. We postulate that activation of the nuclear receptor PPARδ by COX-2-derived prostanoids may be involved in the proliferation of mammary epithelial cells and therefore contribute to mammary cancer development.

Original languageEnglish (US)
Pages (from-to)97-100
Number of pages4
JournalProstaglandins and Other Lipid Mediators
Issue number3-4
StatePublished - Apr 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology


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