TGFβ2 and GDF10 induced dormancy through TGFβRIII to activate phospho-p38MAPK, which phosphorylates retinoblastoma (RB) at the novel N-terminal S249/T252 sites to block prostate cancer cell proliferation.
Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts.
Herein, we developed, optimized and standardized a multiplex MethyLight assay to simultaneously detect hypermethylation of APC, HOXD3 and TGFB2 in DNA extracted from prostate cancer (PCa) cell lines, archival tissue specimens, and urine samples.
To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors beta 1 (TGF-beta 1), TGF-beta 2 and TGF-beta 3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer.
Based on these results we addressed the question of whether TGF beta-2 represented a marker of (anti)androgen action in prostate cancer in vivo: expression of TGF beta mRNA was determined by RNAase protection analysis in normal and malignant prostate tissue obtained from 9 prostate carcinoma patients without endocrine therapy.
TGF-beta 2 induction was only weakly enhanced by cycloheximide and was completely inhibited by actinomycin D. These data show that Bt2-cAMP induces the expression of active TGF-beta 2 by PC-3 prostate carcinoma cells, suggesting a new approach to the treatment of prostate cancer and a new molecular mechanism of cAMP action.