Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)-TGF-? type II dominant negative receptor

Kundu, Shilajit; Kim, Isaac Y.; Yang, Tony T.; Doglio, Lynn; Lang, Sharon; Zhang, Xeujen; Buttyan, Ralph; Kim, Seong‐Jin; Chang, Jay; Cai, Xiaoyan; Wang, Zhou; Lee, Chung

doi:10.1002/(sici)1097-0045(20000501)43:2<118::aid-pros6>3.0.co;2-v

Cited by 36 publications

(14 citation statements)

References 8 publications

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“…Corresponding with this, a gradient in TGF-b expression has been shown to exist, with lowest expression in distal regions of ducts. 61 Furthermore, the absence of either TGF-b 62 or the TGF-b type II receptor (TbRII) 63 induces excessive prostatic epithelial growth and, in the case of TbRII, neoplasias.…”

Section: Tgf-bmentioning

confidence: 99%

Epithelial stem cells in human prostate growth and disease

Hudson

2004

Prostate Cancer Prostatic Dis

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Section: Tgf-bmentioning

confidence: 99%

Epithelial stem cells in human prostate growth and disease

Hudson

2004

Prostate Cancer Prostatic Dis

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“…A number of recent animal studies strongly support that TGF-b can function to suppress tumorigenesis of prostate epithelium (Tang et al, 1999;Song et al, 2000;Bhowmick et al, 2004). Loss of expression for TGF-b receptors can be seen in prostate cancer cells, and restoration of TGF-b receptors reduces tumorigenesis (Kim et al, 1996;Guo et al, 1997;Kyprianou, 1998, 1999;Kundu et al, 2000). To search for genes that modulate TGF-b-induced growth inhibition and apoptosis of prostate cancer cells, we have infected NRP-154 prostate cells with high-complexity retroviral cDNA expression libraries and selected for rare variants resistant to TGF-b-induced growth inhibition and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-β/Smad-induced growth arrest of prostate cells

et al. 2006

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Transforming growth factor-b (TGF-b) elicits a potent growth inhibitory effect on many normal cells by binding to specific serine/threonine kinase receptors and activating specific Smad proteins, which regulate the expression of cell cycle genes, including the p21 cyclin-dependent kinase (CDK) inhibitor gene. Interestingly, cancer cells are often insensitive to the anti-mitogenic effects of TGF-b for which the molecular mechanisms are not well understood. In this study, we found that the candidate prostate cancer susceptibility gene ELAC2 potentiates TGF-b/Smadinduced transcriptional responses. ELAC2 associates with activated Smad2; the C-terminal MH2 domain of Smad2 interacts with the N-terminal region of ELAC2. Small interfering siRNA-mediated knock-down of ELAC2 in prostate cells suppressed TGF-b-induced growth arrest. Moreover, ELAC2 was shown to specifically associate with the nuclear Smad2 partner, FAST-1 and to potentiate the interaction of activated Smad2 with transcription factor Sp1. Furthermore, activation of the p21 CDK inhibitor promoter by TGF-b is potentiated by ELAC2. Taken together our data indicate an important transcriptional scaffold function for ELAC2 in TGF-b/ Smad signaling mediated growth arrest.

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“…Additionally, there is a concomitant increase in the expression of the RI and RII subunits of the TGFh1 receptor (6), as well as phosphorylated Smad2, a key downstream mediator of TGFh1 (4). A dominant negative form of TGFh-RII blocks TGFh1-induced differentiation and cell death (7,8). Finally, administration of TGFh1 to rats results in the apoptosis of the prostate (5,9).…”

Section: Introductionmentioning

confidence: 99%

FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells

Nastiuk

Yoo

et al. 2008

Molecular Cancer Research

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Androgen withdrawal induces the regression of human prostate cancers, but such cancers eventually become androgen-independent and metastasize. Thus, deciphering the mechanism of androgen withdrawalinduced apoptosis is critical to designing new therapies for prostate cancer. Previously, we showed that in the rat, castration-induced apoptosis is accompanied by a reduction in the expression of the apical caspase inhibitor FLICE-like inhibitory protein (FLIP). To test the functional role of FLIP in inhibiting prostate epithelial cell apoptosis, we employed the rat prostate epithelial cell line NRP-152, which differentiates to a secretory phenotype in a low-mitogen medium and then undergoes apoptosis following the addition of transforming growth factor B1 (TGFB1), mimicking androgen withdrawal -induced apoptosis. FLIP levels decline with TGFB1 treatment, suggesting that apoptosis is mediated by caspase-8 and indeed the caspase inhibitor crmA blocks TGFB1-induced apoptosis. Small interfering RNA -mediated knockdown of FLIP recapitulates and enhances TGFB1-induced cell death. NRP-152 cells stably transfected with constitutively expressed FLIP were refractory to TGFB1-induced apoptosis. TGFB1-induced caspase-3 activity is proportional to the level of cell death and inversely proportional to the level of FLIP expression in various clones. Moreover, neither caspase-3 nor PARP is cleaved in clones expressing high levels of FLIP. Furthermore, insulin, which inhibits differentiation, increases FLIP and inhibits TGFB-induced death in a FLIP-dependent manner. Although neither Fas-Fc, sTNFRII-Fc, nor DR5-Fc blocked TGFB1-induced cell death, there is a significant increase in tumor necrosis factor mRNA following TGFB stimulation, suggesting both an unexpected role for tumor necrosis factor in this model system and the possibility that FLIP blocks another unknown caspase-dependent mediator of apoptosis. (Mol Cancer Res 2008;6(2):231 -42)

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Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)-TGF-? type II dominant negative receptor

Cited by 36 publications

References 8 publications

Epithelial stem cells in human prostate growth and disease

Epithelial stem cells in human prostate growth and disease

ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-β/Smad-induced growth arrest of prostate cells

FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells

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