| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Ludwig Institute for Cancer Research, Biomedical Center, SE-751 24 Uppsala [G. B., P. t. D., C-H. H., M. L.], and Institute of Anatomy and Cell Biology, Göteborg University, SE-405 30 Göteborg [K. F.], Sweden
Transforming growth factor (TGF)-ß1 is induced in the prostate after castration and has been implicated in apoptosis of epithelial cells during involution. TGF-ß1-mediated receptor activation induces phosphorylation of Smad2 and Smad3, which form complexes with Smad4, that translocate to the nucleus to regulate transcription of target genes. Smad6 and Smad7 antagonize the action of signal-transducing Smads.
We have examined the immunohistochemical expression of different Smad molecules in the epithelium of rat ventral prostate before and after castration, in androgen-sensitive Dunning R3327 PAP prostatic tumor cells from untreated and castrated rats, and after treatment with estrogen. In the ventral prostate, a significant increase of phosphorylated Smad2 (P-Smad2) was observed after castration. In prostatic tumor cells we observed an increased expression of Smad2 and P-Smad2 after treatment. The levels of Smad3 and, in particular, Smad4 were enhanced in the normal ventral prostate, as well as in the tumors after castration. Interestingly, Smad6 and Smad7 expression was also up-regulated in cells with increased Smad2 activation. The staining for Smad2, P-Smad2, Smad3, Smad4, and Smad7 was nuclear in some cells and was present in areas with a large number of apoptotic cells identified by various morphological criteria, formation of apoptotic bodies and, in adjacent sections, by terminal deoxynucleotidyl transferase-mediated nick end labeling assay.
Our results suggest that the signal transduction pathway for TGF-ß, leading to apoptosis, is activated in the normal prostate after castration and in the tumor model after castration, without or with estrogen treatment.
This article has been cited by other articles:
|
|
 |
|
  K. Song, H. Wang, T. L. Krebs, S.-J. Kim, and D. Danielpour Androgenic Control of Transforming Growth Factor-{beta} Signaling in Prostate Epithelial Cells through Transcriptional Suppression of Transforming Growth Factor-{beta} Receptor II Cancer Res., October 1, 2008; 68(19): 8173 - 8182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. R. Placencio, A.-R. Sharif-Afshar, X. Li, H. Huang, C. Uwamariya, E. G. Neilson, M. M. Shen, R. J. Matusik, S. W. Hayward, and N. A. Bhowmick Stromal Transforming Growth Factor-{beta} Signaling Mediates Prostatic Response to Androgen Ablation by Paracrine Wnt Activity Cancer Res., June 15, 2008; 68(12): 4709 - 4718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Nastiuk, K. Yoo, K. Lo, K. Su, P. Yeung, J. Kutaka, D. Danielpour, and J. J. Krolewski FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor {beta}1-Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells Mol. Cancer Res., February 1, 2008; 6(2): 231 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lu, J. Lee, M. Revelo, X. Wang, S. Lu, and Z. Dong Smad3 Is Overexpressed in Advanced Human Prostate Cancer and Necessary for Progressive Growth of Prostate Cancer Cells in Nude Mice Clin. Cancer Res., October 1, 2007; 13(19): 5692 - 5702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Gilliver, J. J. Ashworth, S. J. Mills, M. J. Hardman, and G. S. Ashcroft Androgens modulate the inflammatory response during acute wound healing J. Cell Sci., February 15, 2006; 119(4): 722 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Moren, T. Imamura, K. Miyazono, C.-H. Heldin, and A. Moustakas Degradation of the Tumor Suppressor Smad4 by WW and HECT Domain Ubiquitin Ligases J. Biol. Chem., June 10, 2005; 280(23): 22115 - 22123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, K. Song, T. L. Sponseller, and D. Danielpour Novel Function of Androgen Receptor-associated Protein 55/Hic-5 as a Negative Regulator of Smad3 Signaling J. Biol. Chem., February 18, 2005; 280(7): 5154 - 5162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Edlund, S. Y. Lee, S. Grimsby, S. Zhang, P. Aspenstrom, C.-H. Heldin, and M. Landstrom Interaction between Smad7 and {beta}-Catenin: Importance for Transforming Growth Factor {beta}-Induced Apoptosis Mol. Cell. Biol., February 15, 2005; 25(4): 1475 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Song, S. C. Cornelius, M. Reiss, and D. Danielpour Insulin-like Growth Factor-I Inhibits Transcriptional Responses of Transforming Growth Factor-{beta} by Phosphatidylinositol 3-Kinase/Akt-dependent Suppression of the Activation of Smad3 but Not Smad2 J. Biol. Chem., October 3, 2003; 278(40): 38342 - 38351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Liu, A. R. Bauskin, J. Zaunders, D. A. Brown, S. Pankurst, P. J. Russell, and S. N. Breit Macrophage Inhibitory Cytokine 1 Reduces Cell Adhesion and Induces Apoptosis in Prostate Cancer Cells Cancer Res., August 15, 2003; 63(16): 5034 - 5040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Song, S. C. Cornelius, and D. Danielpour Development and Characterization of DP-153, a Nontumorigenic Prostatic Cell Line That Undergoes Malignant Transformation by Expression of Dominant-negative Transforming Growth Factor {beta} Receptor Type II Cancer Res., August 1, 2003; 63(15): 4358 - 4367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Wildey, S. Patil, and P. H. Howe Smad3 Potentiates Transforming Growth Factor beta (TGFbeta )-induced Apoptosis and Expression of the BH3-only Protein Bim in WEHI 231 B Lymphocytes J. Biol. Chem., May 9, 2003; 278(20): 18069 - 18077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, X. Luo, and N. Chegini Differential Expression, Regulation, and Induction of Smads, Transforming Growth Factor-{beta} Signal Transduction Pathway in Leiomyoma, and Myometrial Smooth Muscle Cells and Alteration by Gonadotropin-Releasing Hormone Analog J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1350 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Kang, K.-E. Huang, S. Y. Chang, W.-L. Ma, W.-J. Lin, and C. Chang Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4 J. Biol. Chem., November 8, 2002; 277(46): 43749 - 43756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schiffer, L. E. Schiffer, A. Gupta, A. S. Shaw, I. S.D. Roberts, P. Mundel, and E. P. Bottinger Inhibitory Smads and TGF-{beta} Signaling in Glomerular Cells J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2657 - 2666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ostendorf, U. Kunter, C. van Roeyen, S. Dooley, N. Janjic, J. Ruckman, F. Eitner, and J. Floege The Effects of Platelet-Derived Growth Factor Antagonism in Experimental Glomerulonephritis Are Independent of the Transforming Growth Factor-{beta} System J. Am. Soc. Nephrol., March 1, 2002; 13(3): 658 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Bruckheimer and N. Kyprianou Dihydrotestosterone Enhances Transforming Growth Factor-{beta}-Induced Apoptosis in Hormone-Sensitive Prostate Cancer Cells Endocrinology, June 1, 2001; 142(6): 2419 - 2426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hayes, M. Zarnegar, M. Sharma, F. Yang, D. M. Peehl, P. t. Dijke, and Z. Sun SMAD3 Represses Androgen Receptor-mediated Transcription Cancer Res., March 1, 2001; 61(5): 2112 - 2118. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. P. de Caestecker, E. Piek, and A. B. Roberts Role of Transforming Growth Factor-{beta} Signaling in Cancer J Natl Cancer Inst, September 6, 2000; 92(17): 1388 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nakao, S. Miike, M. Hatano, K. Okumura, T. Tokuhisa, C. Ra, and I. Iwamoto Blockade of Transforming Growth Factor {beta}/Smad Signaling in T Cells by Overexpression of Smad7 Enhances Antigen-induced Airway Inflammation and Airway Reactivity J. Exp. Med., July 10, 2000; 192(2): 151 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Monroe, D. F. Jin, and M. M. Sanders Estrogen Opposes the Apoptotic Effects of Bone Morphogenetic Protein 7 on Tissue Remodeling Mol. Cell. Biol., July 1, 2000; 20(13): 4626 - 4634. [Abstract] [Full Text]
|
|
|
|
|
|
G. Brodin, A. Ahgren, P. ten Dijke, C.-H. Heldin, and R. Heuchel Efficient TGF-beta Induction of the Smad7 Gene Requires Cooperation between AP-1, Sp1, and Smad Proteins on the Mouse Smad7 Promoter J. Biol. Chem., September 8, 2000; 275(37): 29023 - 29030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Patil, G. M. Wildey, T. L. Brown, L. Choy, R. Derynck, and P. H. Howe Smad7 Is Induced by CD40 and Protects WEHI 231 B-lymphocytes from Transforming Growth Factor-beta -induced Growth Inhibition and Apoptosis J. Biol. Chem., December 1, 2000; 275(49): 38363 - 38370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jornvall, A. Blokzijl, P. t. Dijke, and C. F. Ibanez The Orphan Receptor Serine/Threonine Kinase ALK7 Signals Arrest of Proliferation and Morphological Differentiation in a Neuronal Cell Line J. Biol. Chem., February 9, 2001; 276(7): 5140 - 5146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamamura, X. Hua, S. Bergelson, and H. F. Lodish Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-beta -dependent Apoptosis J. Biol. Chem., November 10, 2000; 275(46): 36295 - 36302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Chipuk, M. Bhat, A. Y. Hsing, J. Ma, and D. Danielpour Bcl-xL Blocks Transforming Growth Factor-beta 1-induced Apoptosis by Inhibiting Cytochrome c Release and Not by Directly Antagonizing Apaf-1-dependent Caspase Activation in Prostate Epithelial Cells J. Biol. Chem., July 6, 2001; 276(28): 26614 - 26621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Chipuk, S. C. Cornelius, N. J. Pultz, J. S. Jorgensen, M. J. Bonham, S.-J. Kim, and D. Danielpour The Androgen Receptor Represses Transforming Growth Factor-beta Signaling through Interaction with Smad3 J. Biol. Chem., January 4, 2002; 277(2): 1240 - 1248. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
