| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,2
* Division of Biomedical Sciences, University of California, Riverside, California 92521;
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089–9112; and
Epiclone Inc., Alhambra, California 91801
The aim of this review is to provide insight into the molecular mechanisms by which activin A modulates cell proliferation, apoptosis, and carcinogenesis in vitro and in vivo. Activin A, a member of the TGFß superfamily, has various effects on diverse biological systems, including cell growth inhibition in many cell types. However, the mechanism(s) by which activin exerts its inhibitory effects are not yet understood. This review highlights activin's effects on activin receptors and signaling pathway, modulation of activin signaling, and regulation of cell proliferation and apoptosis by activin. Based on the experiences of all the authors, we emphasized cell cycle inhibitors such as p16 and p21 and regulators of apoptosis such as p53 and members of the bcl-2 family. Aside from activin's inhibition of cell proliferation and enhancement of apoptosis, other newly developed methods for molecular studies of apoptosis by activin were briefly presented that support the role of activin as an inhibitor of carcinogenesis and cancer progression. These methods include subtractive hybridization based on covalent bonding, a simple and accurate means to determine molecular profile of as few as 20 cells based on an RNA-PCR approach, and a messenger RNA-antisense DNA interference phenomenon (D-RNAi), resulting in a long-term gene knockout effects.
Key Words: activin • activin receptors • Smad • activin-binding protein • signaling pathway • cell proliferation • apoptosis • carcinogenesis • subtractive hybridization • RNA-PCR • D-RNAi
This article has been cited by other articles:
|
|
 |
|
  N. C. Robson, D. J. Phillips, T. McAlpine, A. Shin, S. Svobodova, T. Toy, V. Pillay, N. Kirkpatrick, D. Zanker, K. Wilson, et al. Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production Blood, March 1, 2008; 111(5): 2733 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Korupolu, U. Muenster, J. D. Read, W. Vale, and W. H. Fischer Activin A/Bone Morphogenetic Protein (BMP) Chimeras Exhibit BMP-like Activity and Antagonize Activin and Myostatin J. Biol. Chem., February 15, 2008; 283(7): 3782 - 3790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-L. Lin, D. Chang, A. Chiang, and S.-Y. Ying Androgen receptor regulates CD168 expression and signaling in prostate cancer Carcinogenesis, February 1, 2008; 29(2): 282 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ogino, S. Yano, S. Kakiuchi, H. Muguruma, K. Ikuta, M. Hanibuchi, H. Uehara, K. Tsuchida, H. Sugino, and S. Sone Follistatin Suppresses the Production of Experimental Multiple-Organ Metastasis by Small Cell Lung Cancer Cells in Natural Killer Cell-Depleted SCID Mice Clin. Cancer Res., February 1, 2008; 14(3): 660 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Razanajaona, S. Joguet, A.-S. Ay, I. Treilleux, S. Goddard-Leon, L. Bartholin, and R. Rimokh Silencing of FLRG, an Antagonist of Activin, Inhibits Human Breast Tumor Cell Growth Cancer Res., August 1, 2007; 67(15): 7223 - 7229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-L. Lin, D. Chang, and S.-Y. Ying Hyaluronan stimulates transformation of androgen-independent prostate cancer Carcinogenesis, February 1, 2007; 28(2): 310 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, J. S. Bailey, D. Coss, B. Lin, R. Tsutsumi, M. A. Lawson, P. L. Mellon, and N. J. G. Webster Activin Modulates the Transcriptional Response of L{beta}T2 Cells to Gonadotropin-Releasing Hormone and Alters Cellular Proliferation Mol. Endocrinol., November 1, 2006; 20(11): 2909 - 2930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Krneta, J. Kroll, F. Alves, C. Prahst, F. Sananbenesi, C. Dullin, S. Kimmina, D. J. Phillips, and H. G. Augustin Dissociation of Angiogenesis and Tumorigenesis in Follistatin- and Activin-Expressing Tumors Cancer Res., June 1, 2006; 66(11): 5686 - 5695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-G. Chen, Q. Wang, S.-L. Lin, C. D. Chang, J. Chung, and S.-Y. Ying Activin Signaling and Its Role in Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis. Experimental Biology and Medicine, May 1, 2006; 231(5): 534 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Muenster, C. A. Harrison, C. Donaldson, W. Vale, and W. H. Fischer An Activin-A/C Chimera Exhibits Activin and Myostatin Antagonistic Properties J. Biol. Chem., November 4, 2005; 280(44): 36626 - 36632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, M. Nomura, H. Morinaga, E. Matsubara, T. Okabe, K. Goto, T. Yanase, H. Zheng, J. Lu, and H. Nawata Modulation of Androgen Receptor Transactivation by FoxH1: A NEWLY IDENTIFIED ANDROGEN RECEPTOR COREPRESSOR J. Biol. Chem., October 28, 2005; 280(43): 36355 - 36363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Burdette, J. S. Jeruss, S. J. Kurley, E. J. Lee, and T. K. Woodruff Activin A Mediates Growth Inhibition and Cell Cycle Arrest through Smads in Human Breast Cancer Cells Cancer Res., September 1, 2005; 65(17): 7968 - 7975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zalzman, L. Anker-Kitai, and S. Efrat Differentiation of Human Liver-Derived, Insulin-Producing Cells Toward the {beta}-Cell Phenotype Diabetes, September 1, 2005; 54(9): 2568 - 2575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E J Gold, X Zhang, A M Wheatley, S L Mellor, M Cranfield, G P Risbridger, N P Groome, and J S Fleming {beta}A- and {beta}C-activin, follistatin, activin receptor mRNA and {beta}C-activin peptide expression during rat liver regeneration J. Mol. Endocrinol., April 1, 2005; 34(2): 505 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Panopoulou, C. Murphy, H. Rasmussen, E. Bagli, E. K. Rofstad, and T. Fotsis Activin A Suppresses Neuroblastoma Xenograft Tumor Growth via Antimitotic and Antiangiogenic Mechanisms Cancer Res., March 1, 2005; 65(5): 1877 - 1886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Steller, T. J. Shaw, B. C. Vanderhyden, and J.-F. Ethier Inhibin Resistance Is Associated with Aggressive Tumorigenicity of Ovarian Cancer Cells Mol. Cancer Res., January 1, 2005; 3(1): 50 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Deacu, Y. Mori, F. Sato, J. Yin, A. Olaru, A. Sterian, Y. Xu, S. Wang, K. Schulmann, A. Berki, et al. Activin Type II Receptor Restoration in ACVR2-Deficient Colon Cancer Cells Induces Transforming Growth Factor-{beta} Response Pathway Genes Cancer Res., November 1, 2004; 64(21): 7690 - 7696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Smith, A. Yndestad, B. Halvorsen, T. Ueland, T. Waehre, K. Otterdal, H. Scholz, K. Endresen, L. Gullestad, S. S. Froland, et al. Potential anti-inflammatory role of activin A in acute coronary syndromes J. Am. Coll. Cardiol., July 21, 2004; 44(2): 369 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Harrison, P. C. Gray, W. H. Fischer, C. Donaldson, S. Choe, and W. Vale An Activin Mutant with Disrupted ALK4 Binding Blocks Signaling via Type II Receptors J. Biol. Chem., July 2, 2004; 279(27): 28036 - 28044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. X. Xing, X. F. Hu, G. A. Pietersz, H. L. Hosick, and I. F. C. McKenzie Cripto: A Novel Target for Antibody-Based Cancer Immunotherapy Cancer Res., June 1, 2004; 64(11): 4018 - 4023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Borawski, B. Naumnik, and M. Mysliwiec Activin A/Follistatin System: Another Link to Heparin-induced Osteoporosis? Clinical and Applied Thrombosis/Hemostasis, April 1, 2004; 10(2): 191 - 192. [PDF]
|
|
|
|
 |
|
 A. Yndestad, T. Ueland, E. Oie, G. Florholmen, B. Halvorsen, H. Attramadal, S. Simonsen, S. S. Froland, L. Gullestad, G. Christensen, et al. Elevated Levels of Activin A in Heart Failure: Potential Role in Myocardial Remodeling Circulation, March 23, 2004; 109(11): 1379 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Carey, L. M. Sasur, H. Kawakubo, V. Gupta, B. Christian, P. M. Bailey, and S. Maheswaran Mutually Antagonistic Effects of Androgen and Activin in the Regulation of Prostate Cancer Cell Growth Mol. Endocrinol., March 1, 2004; 18(3): 696 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Beuschlein, B. D. Looyenga, S. E. Bleasdale, C. Mutch, D. L. Bavers, A. F. Parlow, J. H. Nilson, and G. D. Hammer Activin Induces x-Zone Apoptosis That Inhibits Luteinizing Hormone-Dependent Adrenocortical Tumor Formation in Inhibin-Deficient Mice Mol. Cell. Biol., June 1, 2003; 23(11): 3951 - 3964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Harrison, P. C. Gray, S. C. Koerber, W. Fischer, and W. Vale Identification of a Functional Binding Site for Activin on the Type I Receptor ALK4 J. Biol. Chem., May 30, 2003; 278(23): 21129 - 21135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dupont, J. McNeilly, A. Vaiman, S. Canepa, Y. Combarnous, and C. Taragnat Activin Signaling Pathways in Ovine Pituitary and L{beta}T2 Gonadotrope Cells Biol Reprod, May 1, 2003; 68(5): 1877 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Gray, C. A. Harrison, and W. Vale Cripto forms a complex with activin and type II activin receptors and can block activin signaling PNAS, April 29, 2003; 100(9): 5193 - 5198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Fleet, L. Wang, O. Vitek, B. A. Craig, and H. J. Edenberg Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation Physiol Genomics, March 18, 2003; 13(1): 57 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Shin, H. Wang, A. M. Yim, F. Le Naour, F. Brichory, J. H. Jang, R. Zhao, E. Puravs, J. Tra, C. W. Michael, et al. Global Profiling of the Cell Surface Proteome of Cancer Cells Uncovers an Abundance of Proteins with Chaperone Function J. Biol. Chem., February 21, 2003; 278(9): 7607 - 7616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Danila, X. Zhang, Y. Zhou, J. N. S. Haidar, and A. Klibanski Overexpression of Wild-Type Activin Receptor Alk4-1 Restores Activin Antiproliferative Effects in Human Pituitary Tumor Cells J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4741 - 4746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Bacolod, S. P. Johnson, F. Ali-Osman, P. Modrich, N. S. Bullock, O. M. Colvin, D. D. Bigner, and H. S. Friedman Mechanisms of Resistance to 1,3-Bis(2-chloroethyl)-1-nitrosourea in Human Medulloblastoma and Rhabdomyosarcoma Mol. Cancer Ther., July 1, 2002; 1(9): 727 - 736. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
