SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Qiang, Y.-W. Articles by Rudikoff, S. Search for Related Content PubMed PubMed Citation Articles by Qiang, Y.-W. Articles by Rudikoff, S. Related Collections Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2002, Vol. 99, No. 11, pp. 4138-4146 NEOPLASIA Insulinlike growth factor-I signaling in multiple myeloma: downstream elements, functional correlates, and pathway cross-talk Ya-Wei Qiang, Eugene Kopantzev, and Stuart Rudikoff From the Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD. In multiple myeloma cells, insulinlike growth factor-I (IGF-I) activates 2 distinct signaling pathways, mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI-3K), leading to both proliferative and antiapoptotic effects. However, it is unclear through which of these cascades IGF-I regulates these different responses. The present studies identify a series of downstream targets in the PI-3K pathway, including glycogen synthase kinase-3, p70S6 kinase, and the 3 members of the Forkhead family of transcription factors. The contribution of the MAPK and PI-3K pathways and, where possible, individual elements to proliferation and apoptosis was evaluated by means of a series of specific kinase inhibitors. Both processes were regulated almost exclusively by the PI-3K pathway, with only minor contributions associated with the MAPK cascade. Within the PI-3K cascade, inhibition of p70S6 kinase led to significant decreases in proliferation and protection from apoptosis. Activation of p70S6 kinase could also be prevented by MAPK inhibitors, indicating regulation by both pathways. The Forkhead transcription factor FKHRL1 was observed to provide a dual effect in that phosphorylation upon IGF-I treatment resulted in a loss of ability to inhibit proliferation and induce apoptosis. The PI-3K pathway was additionally shown to exhibit cross-talk and to regulate the MAPK cascade, as inhibition of PI-3K prevented activation of Mek1/2 and other downstream MAPK elements. These results define important elements in IGF-I regulation of myeloma cell growth and provide biological correlates critical to an understanding of growth-factor modulation of proliferation and apoptosis. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Hu, K. Kirito, K. Yoshida, T. Mitsumori, K. Nakajima, Y. Nozaki, S. Hamanaka, T. Nagashima, M. Kunitama, K. Sakoe, et al. Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan Mol. Cancer Ther., August 1, 2009; 8(8): 2329 - 2338. [Abstract] [Full Text] [PDF] Y.-W. Qiang, B. Hu, Y. Chen, Y. Zhong, B. Shi, B. Barlogie, and J. D. Shaughnessy Jr Bortezomib induces osteoblast differentiation via Wnt-independent activation of {beta}-catenin/TCF signaling Blood, April 30, 2009; 113(18): 4319 - 4330. [Abstract] [Full Text] [PDF] J.-E. Choi, S.-s. Lee, D. A. Sunde, I. Huizar, K. L. Haugk, V. J. Thannickal, R. Vittal, S. R. Plymate, and L. M. Schnapp Insulin-like Growth Factor-I Receptor Blockade Improves Outcome in Mouse Model of Lung Injury Am. J. Respir. Crit. Care Med., February 1, 2009; 179(3): 212 - 219. [Abstract] [Full Text] [PDF] B. M. Birmann, R. M. Tamimi, E. Giovannucci, B. Rosner, D. J. Hunter, P. Kraft, C. Mitsiades, K. C. Anderson, and G. A. Colditz Insulin-like Growth Factor-1- and Interleukin-6-related Gene Variation and Risk of Multiple Myeloma Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 282 - 288. [Abstract] [Full Text] [PDF] Y.-W. Qiang, J. D. Shaughnessy Jr, and S. Yaccoby Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth Blood, July 15, 2008; 112(2): 374 - 382. [Abstract] [Full Text] [PDF] Y.-W. Qiang, Y. Chen, O. Stephens, N. Brown, B. Chen, J. Epstein, B. Barlogie, and J. D. Shaughnessy Jr Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma Blood, July 1, 2008; 112(1): 196 - 207. [Abstract] [Full Text] [PDF] J. C. Montero, R. Lopez-Perez, J. F. San Miguel, and A. Pandiella Expression of c-Kit isoforms in multiple myeloma: differences in signaling and drug sensitivity Haematologica, June 1, 2008; 93(6): 851 - 859. [Abstract] [Full Text] [PDF] J. Yang, X. Zhang, J. Wang, J. Qian, L. Zhang, M. Wang, L. W. Kwak, and Q. Yi Anti {beta}2-microglobulin monoclonal antibodies induce apoptosis in myeloma cells by recruiting MHC class I to and excluding growth and survival cytokine receptors from lipid rafts Blood, October 15, 2007; 110(8): 3028 - 3035. [Abstract] [Full Text] [PDF] H. Chen, M. S. Gordon, R. A. Campbell, M. Li, C. S. Wang, H. J. Lee, E. Sanchez, S. J. Manyak, D. Gui, D. Shalitin, et al. Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth Blood, July 1, 2007; 110(1): 287 - 295. [Abstract] [Full Text] [PDF] E. Menu, H. Jernberg-Wiklund, T. Stromberg, H. De Raeve, L. Girnita, O. Larsson, M. Axelson, K. Asosingh, K. Nilsson, B. Van Camp, et al. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model Blood, January 15, 2006; 107(2): 655 - 660. [Abstract] [Full Text] [PDF] T. Stromberg, S. Ekman, L. Girnita, L. Y. Dimberg, O. Larsson, M. Axelson, J. Lennartsson, U. Hellman, K. Carlson, A. Osterborg, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells Blood, January 15, 2006; 107(2): 669 - 678. [Abstract] [Full Text] [PDF] Y.-W. Qiang, K. Walsh, L. Yao, N. Kedei, P. M. Blumberg, J. S. Rubin, J. Shaughnessy Jr, and S. Rudikoff Wnts induce migration and invasion of myeloma plasma cells Blood, September 1, 2005; 106(5): 1786 - 1793. [Abstract] [Full Text] [PDF] X. Carvajal-Vergara, S. Tabera, J. C. Montero, A. Esparis-Ogando, R. Lopez-Perez, G. Mateo, N. Gutierrez, M. Parmo-Cabanas, J. Teixido, J. F. San Miguel, et al. Multifunctional role of Erk5 in multiple myeloma Blood, June 1, 2005; 105(11): 4492 - 4499. [Abstract] [Full Text] [PDF] K. Ghias, C. Ma, V. Gandhi, L. C. Platanias, N. L. Krett, and S. T. Rosen 8-Amino-adenosine induces loss of phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, and Akt kinase: Role in induction of apoptosis in multiple myeloma Mol. Cancer Ther., April 1, 2005; 4(4): 569 - 577. [Abstract] [Full Text] [PDF] N. W.C.J. van de Donk, H. M. Lokhorst, E. H.J. Nijhuis, M. M.J. Kamphuis, and A. C. Bloem Geranylgeranylated Proteins are Involved in the Regulation of Myeloma Cell Growth Clin. Cancer Res., January 15, 2005; 11(2): 429 - 439. [Abstract] [Full Text] [PDF] N. Raje, S. Kumar, T. Hideshima, K. Ishitsuka, D. Chauhan, C. Mitsiades, K. Podar, S. Le Gouill, P. Richardson, N. C. Munshi, et al. Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma Blood, December 15, 2004; 104(13): 4188 - 4193. [Abstract] [Full Text] [PDF] T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson Advances in biology of multiple myeloma: clinical applications Blood, August 1, 2004; 104(3): 607 - 618. [Abstract] [Full Text] [PDF] T. Stromberg, A. Dimberg, A. Hammarberg, K. Carlson, A. Osterborg, K. Nilsson, and H. Jernberg-Wiklund Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone Blood, April 15, 2004; 103(8): 3138 - 3147. [Abstract] [Full Text] [PDF] J. Moreaux, E. Legouffe, E. Jourdan, P. Quittet, T. Reme, C. Lugagne, P. Moine, J.-F. Rossi, B. Klein, and K. Tarte BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone Blood, April 15, 2004; 103(8): 3148 - 3157. [Abstract] [Full Text] [PDF] K. Mahtouk, M. Jourdan, J. De Vos, C. Hertogh, G. Fiol, E. Jourdan, J.-F. Rossi, and B. Klein An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis Blood, March 1, 2004; 103(5): 1829 - 1837. [Abstract] [Full Text] [PDF] Y.-W. Qiang, L. Yao, G. Tosato, and S. Rudikoff Insulin-like growth factor I induces migration and invasion of human multiple myeloma cells Blood, January 1, 2004; 103(1): 301 - 308. [Abstract] [Full Text] [PDF] J. Shaughnessy Jr Primer on Medical Genomics Part IX: Scientific and Clinical Applications of DNA Microarrays--Multiple Myeloma as a Disease Model Mayo Clin. Proc., September 1, 2003; 78(9): 1098 - 1109. [Abstract] [PDF] L. Drucker, O. Uziel, T. Tohami, H. Shapiro, J. Radnay, S. Yarkoni, M. Lahav, and M. Lishner Thalidomide Down-Regulates Transcript Levels of GC-Rich Promoter Genes in Multiple Myeloma Mol. Pharmacol., August 1, 2003; 64(2): 415 - 420. [Abstract] [Full Text] [PDF] L. C. Platanias Map kinase signaling pathways and hematologic malignancies Blood, June 15, 2003; 101(12): 4667 - 4679. [Abstract] [Full Text] [PDF] J. Shaughnessy, J. Jacobson, J. Sawyer, J. McCoy, A. Fassas, F. Zhan, K. Bumm, J. Epstein, E. Anaissie, S. Jagannath, et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression Blood, May 15, 2003; 101(10): 3849 - 3856. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020