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My laboratory focuses on the role of transforming growth factor-beta (TGF-ß) as a tumor suppressor and regulator of growth, apoptosis and androgenic responses in the prostate. TGF-ßs are a family of 25 kDa dimeric regulatory peptides that function as autocrine, paracrine and possibly endocrine regulators of growth, apoptosis and differentiation in numerous tissues. Signal transduction by these peptides is initiated through two cell surface serine/threonine kinase receptors, TβRII and TβRI. The predominant TGF-β ligand, TGF-β1, first binds to TβRII, which then recruits and activates TβRI by the constitutively active TβRII kinase. The activated TβRI in turn recruits and activates the transcription factors Smads 2 and 3, also known as rSmads. Nuclear targeting sequences exposed upon activation of rSmads promote their nuclear translocation, either in association with Smad4 or without Smad4, thereby enabling transcriptional activation of numerous TGF-β target genes. An important role for TGF-β in the prostate is strongly implicated by a number of in vivo studies, which demonstrate that androgens negatively regulate expression of TGF-βs, TGF-β receptors, and the activation of rSmads in the prostate. In addition, normal cellular responses to TGF-βs in the prostate are lost during carcinogenesis of this tissue concomitant with loss of TGF-β receptor levels and loss of androgen dependence, implicating a role for TGF-β as a tumor suppressor and regulator of androgen dependence. Using primary prostatic cells lines, our laboratory was first to report that TGF- can directly induce apoptosis of prostatic cells in culture, implicating a role of this cytokine in apoptosis of the prostate following androgen ablation. Thus, an important focus of our work is to understand how TGF-β induces apoptosis.
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Current Research in Pharmacology and Drug Discovery (2022): 100117
Current research in pharmacology and drug discovery (2022): 100076
Oncogeneno. 50 (2022): 5411-5412
Biochemical and biophysical research communicationsno. 2 (2019): 374-380
David Danielpour,Zhaofeng Gao, Patrick M. Zmina,Eswar Shankar, Benjamin C. Shultes,Raul Jobava,Scott M. Welford,Maria Hatzoglou
Scientific Reportsno. 1 (2019)
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David Danielpour,Zhaofeng Gao, Patrick M. Zmina,Eswar Shankar, Benjamin C. Shultes,Raul Jobava,Scott M. Welford,Maria Hatzoglou
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