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SMAD-Mediated Signaling During Prostate Growth and Development

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Final rept. 17 Sep 2001-16 Sep 2005

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The binding of TGF-Beta family molecules to their receptors on the surfaces of cells initiates a signaling pathway within the cells. The Smad family of molecules mediates the propagation of the intracellular signal from the receptor for TGF-Beta. Two different Smad molecules are essential to propagating this signal, Smad 2 and Smad 3. It has been shown that Smad 2 expression is altered in prostate cancer and adult normal prostate cells enter programmed cell death with increased Smad 2 expression. In the analysis of prostate development the expression of Smad 2 is increased at the very early stages of gland development in the first 7 days post-natally. The pattern of Smad 2 expression is indicative of TGF-Beta signaling and during early gland formation with cell proliferation. Smad 3 is also expressed in the early stages of gland development and continues to be expressed at late stages of development. Phosphorylation of the Smad molecules is essential to signal propagation and both Smad 2 3 are phosphorylated indicating that TGF-Beta signaling is occurring. Prostate development demonstrates the involvement of the TGF-Beta signaling pathway in mechanisms that stimulate cell division, a process required for tumorigenesis. Differential response of prostate cells based on age of the tissue may indicate changes in response to the growth factors and persistence or reacquisition of the neonatal phenotype may be associated with tumor development. These results on the basic understanding of the signaling pathway will lead to new strategies for therapeutic intervention to alter cell growth and differentiation that may lead to neoplastic events.

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  • Medicine and Medical Research

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