To better model the primarily luminal phenotype of human CaP we mutated Pten and Tgfbr2 specifically in luminal cells, and found that these tumors also progress to invasive and metastatic cancer.
Seventy percent of prostate cancer patients lose expression of transforming growth factor-beta type II receptor (TGFBR2) in the stromal compartment (n=77, P-value=0.0001), similar to the rate of glutathione S-transferase P1 (GSTP1) silencing.
TGFBR2-875G>A polymorphism was studied by allelic discrimination using real-time polymerase chain reaction (PCR) in 891 patients with PC and 874 controls.
Loss of TGF-β type II receptor (TβRII, encoded by Tgfbr2) expression in the prostate stroma contributes to prostate cancer initiation, progression, and invasion.
Among these genes, it appears that: PPARG promotes the PPAR signaling pathway via the upregulation of lipoprotein lipase (LPL) expression, but suppresses the cell cycle pathway via downregulation of growth arrest and DNA-damage-inducible, γ (GADD45G) expression; ETV4 stimulates matrix metallopeptidase 9 (MMP9) expression to induce the bladder cancer pathway; FLI upregulates transforming growth factor, β receptor II (TGFBR2) expression to activate TGF-β signaling and upregulates cyclin D3 (CCND3) expression to promote the cell cycle pathway; NFKB1 upregulates interleukin 1, β (IL-1B) expression and initiates the prostate cancer pathway; CEBPB upregulates IL-6 expression and promotes pathways in cancer; and TAL1 promotes kinase insert domain receptor (KDR) expression to promote the TGF-β signaling pathway.
The identification of methylation silencing of Tgfbr2 in rat prostate cancers, in accordance with TGFBR2 down-regulation in human prostate cancers, will enable us to analyze how aberrant methylation is induced in vivo and identify factors that promote and suppress the induction of aberrant methylation.
Glucocorticoid up-regulates transforming growth factor-beta (TGF-beta) type II receptor and enhances TGF-beta signaling in human prostate cancer PC-3 cells.