Transforming Growth Factor Beta and Prostate Cancer

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Abstract
The TGF-beta superfamily is the most versatile considering the ability of its members to regulate proliferation, growth arrest, differentiation, and apoptosis of prostatic stromal and epithelial cells as well as the formation of osteoblastic metastases. TGF-beta mediated action in prostate cells follows a complex signaling pathway from binding and phosphorylation of receptor type II to the TbetaRI kinase to Smad activation, resulting in ligand-induced transcription. TGF-beta as an indirect tumor suppressor, its role of regulating tumor induction, as well as tumor suppression depending on the tissue microenvironment merits further exploration. The rationale for targeting growth factors and their receptors for therapeutic intervention is based upon the fact that these proteins represent the most proximate component of the signal transduction cascade. The alternate targeting of intracellular effectors in the signal transduction may be thwarted by cross talk between signaling pathways (such as the Smads in a dynamic interplay with the androgen receptor). TGF-beta within the context of its well-documented apoptosis regulatory actions in the prostate and the significance its key receptor TbetaRII as a potential tumor suppressor, provides a highly attractive candidate for such targeting with high clinical significance for the treatment and diagnosis of prostate cancer.