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. Author manuscript; available in PMC: 2013 Jun 26.
Published in final edited form as: Cancer Res. 2009 Jan 15;69(2):687–694. doi: 10.1158/0008-5472.CAN-08-2446

Figure 5.

Figure 5

Schematic of signal transduction in MMTV-Pax8PPARγ mice. Pax8PPARγ is envisioned to act in a dominant-negative fashion to block PPARγ-dependent inactivation of ER through the proteasomal pathway, promote PGC-1 coactivation of ER, and block PPARγ-mediated transactivation of PTEN. Reduced PTEN activates PI3K and Ras/ERK and AKT, which Inhibit GSK3β and activate β-catenin/TCF signaling. ERK may stimulate ER transcription through AP-1 downstream of ERK. Although, ERK is known to phosphorylate and stabilize ER, pSer104/106ER levels were not altered in the mammary gland of MMTV-Pax8PPARγ vs. wild-type mice. ER may also be phosphorylated by AKT and GSK3β (thin lines), but this has not been examined. Activation of ER and PI3K signaling are believed to increase stem and progenitor cell expansion and ER+ tumors following progestin/DMBA carcinogenesis. It is controversial whether mammary stem cells are ER+.