1. Reduction of Sca-1 increases PPARγ expression.
Reduction of Sca-1 increases PPARγ expression. A, 34T mammary tumor cells were transduced with either a GFP shRNA (34T) or a Sca-1 shRNA (D8) and probed by Western blotting for expression of Sca-1, pSer84PPARγ, PPARγ, pERK1/2, ERK1/2, PTEN, and β-actin. Reduction of Sca-1 increased PPARγ and reduced the percentage of pSer84PPARγ and pERK. B, bar graphs of the Western blots shown in A. C, GW7845 increases PPARγ expression. 34T and D8 cells in A were treated overnight with 0.1 μmol/L GW7845. Bar graph indicates that GW7845 enhanced PPARγ levels to a greater extent in D8 cells than in 34T cells. D, effect of proteasome inhibition on pSer84PPARγ and PPARγ expression. 34T and D8 cells were treated overnight with 1 μmol/L lactacystin. Bar graph indicates that PPARγ expression is increased to a greater extent in 34T cells than in D8 cells. E, reduction of Sca-1 increases PTEN and FABP3 mRNA expression. 34T and D8 cells were analyzed for PTEN and FABP3 mRNA levels by qRT-PCR and all values were normalized to actin. There was a significant difference between 34T and D8 cells in PTEN mRNA levels (P < 0.01, N = 3) and FABP3 mRNA levels (P < 0.001, N = 3) by the 2-sided Student t test. F, schematic of the regulation of PPARγ by Sca-1. Sca-1 is envisioned to suppress PTEN in part through ERK-mediated inhibition of PPARγ. Phosphatidylinositol 3-kinase (PI3K)-dependent Ras/ERK signaling results in increased inhibition of PPARγ by ERK-mediated phosphorylation on Ser84, which in turn reduces PTEN transcription. The opposite effect occurs during Sca-1 deficiency, which results in reduced progenitor cell expansion, delayed tumorigenesis and increased sensitivity to PPARγ agonists.
Hongyan Yuan et al. Cancer Prev Res 2012;5:51-60
©2012 by American Association for Cancer Research