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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research

PTTG1 expression is associated with hyperproliferative disease and poor prognosis in multiple myeloma

Authors: Jacqueline E. Noll, Kate Vandyke, Duncan R. Hewett, Krzysztof M. Mrozik, Rachel J. Bala, Sharon A. Williams, Chung H. Kok, Andrew CW Zannettino

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

Background

Multiple myeloma (MM) is an incurable haematological malignancy characterised by the clonal proliferation of malignant plasma cells within the bone marrow. We have previously identified pituitary tumour transforming gene 1 (Pttg1) as a gene that is significantly upregulated in the haematopoietic compartment of the myeloma-susceptible C57BL/KaLwRij mouse strain, when compared with the myeloma-resistant C57BL/6 mouse. Over-expression of PTTG1 has previously been associated with malignant progression and an enhanced proliferative capacity in solid tumours.

Methods

In this study, we investigated PTTG1 gene and protein expression in MM plasma cells from newly diagnosed MM patients. Gene expression profiling was used to identify gene signatures associated with high PTTG1 expression in MM patients. Additionally, we investigated the effect of short hairpin ribonucleic acid (shRNA)-mediated PTTG1 knockdown on the proliferation of the murine myeloma plasma cell line 5TGM1 in vitro and in vivo.

Results

PTTG1 was found to be over-expressed in 36–70 % of MM patients, relative to normal controls, with high PTTG1 expression being associated with poor patient outcomes (hazard ratio 2.49; 95 % CI 1.28 to 4.86; p = 0.0075; log-rank test). In addition, patients with high PTTG1 expression exhibited increased expression of cell proliferation-associated genes including CCNB1, CCNB2, CDK1, AURKA, BIRC5 and DEPDC1. Knockdown of Pttg1 in 5TGM1 cells decreased cellular proliferation, without affecting cell cycle distribution or viability, and decreased expression of Ccnb1, Birc5 and Depdc1 in vitro. Notably, Pttg1 knockdown significantly reduced MM tumour development in vivo, with an 83.2 % reduction in tumour burden at 4 weeks (p < 0.0001, two-way ANOVA).

Conclusions

This study supports a role for increased PTTG1 expression in augmenting tumour development in a subset of MM patients.
Appendix
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Literature
1.
2.
Landgren O, Morgan GJ. Biologic frontiers in multiple myeloma: from biomarker identification to clinical practice. Clin Cancer Res. 2014;20(4):804–13.PubMedCrossRef
3.
4.
5.
Shaughnessy Jr JD, Zhan F, Burington BE, Huang Y, Colla S, Hanamura I, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276–84.PubMedCrossRef
6.
Decaux O, Lode L, Magrangeas F, Charbonnel C, Gouraud W, Jezequel P, et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myelome. J Clin Oncol. 2008;26(29):4798–805.PubMedCrossRef
7.
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122–8.PubMedCentralPubMedCrossRef
8.
Radl J, Hollander CF, van den Berg P, de Glopper E. Idiopathic paraproteinaemia. I. Studies in an animal model—the ageing C57BL/KaLwRij mouse. Clin Exp Immunol. 1978;33(3):395–402.PubMedCentralPubMed
9.
Radl J, Croese JW, Zurcher C, Van den Enden-Vieveen MH, de Leeuw AM. Animal model of human disease. Multiple myeloma. Am J Pathol. 1988;132(3):593–7.PubMedCentralPubMed
10.
Fowler JA, Mundy GR, Lwin ST, Lynch CC, Edwards CM. A murine model of myeloma that allows genetic manipulation of the host microenvironment. Dis Model Mech. 2009;2(11-12):604–11.PubMedCentralPubMedCrossRef
11.
Garrett IR, Dallas S, Radl J, Mundy GR. A murine model of human myeloma bone disease. Bone. 1997;20(6):515–20.PubMedCrossRef
12.
Oyajobi BO, Munoz S, Kakonen R, Williams PJ, Gupta A, Wideman CL, et al. Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging. Mol Cancer Ther. 2007;6(6):1701–8.PubMedCentralPubMedCrossRef
13.
Radl J, De Glopper ED, Schuit HR, Zurcher C. Idiopathic paraproteinemia. II. Transplantation of the paraprotein-producing clone from old to young C57BL/KaLwRij mice. J Immunol. 1979;122(2):609–13.PubMed
14.
Vanderkerken K, De Raeve H, Goes E, Van Meirvenne S, Radl J, Van Riet I, et al. Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse. Br J Cancer. 1997;76(4):451–60.PubMedCentralPubMedCrossRef
15.
Noll JE, Hewett DR, Williams SA, Vandyke K, Kok C, To LB, et al. SAMSN1 is a tumor suppressor gene in multiple myeloma. Neoplasia. 2014;16(7):572–85.PubMedCentralPubMedCrossRef
16.
Noll JE, Williams SA, Tong CM, Wang H, Quach JM, Purton LE, et al. Myeloma plasma cells alter the bone marrow microenvironment by stimulating the proliferation of mesenchymal stromal cells. Haematologica. 2014;99(1):163–71.PubMedCentralPubMedCrossRef
17.
Fowler JA, Lwin ST, Drake MT, Edwards JR, Kyle RA, Mundy GR, et al. Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease. Blood. 2011;118(22):5872–82.PubMedCentralPubMedCrossRef
18.
Saez C, Japon MA, Ramos-Morales F, Romero F, Segura DI, Tortolero M, et al. hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias. Oncogene. 1999;18(39):5473–6.PubMedCrossRef
19.
Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab. 1999;84(2):761–7.PubMedCrossRef
20.
Heaney AP, Singson R, McCabe CJ, Nelson V, Nakashima M, Melmed S. Expression of pituitary-tumour transforming gene in colorectal tumours. Lancet. 2000;355(9205):716–9.PubMedCrossRef
21.
Boelaert K, McCabe CJ, Tannahill LA, Gittoes NJ, Holder RL, Watkinson JC, et al. Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. J Clin Endocrinol Metab. 2003;88(5):2341–7.PubMedCrossRef
22.
Rehfeld N, Geddert H, Atamna A, Rohrbeck A, Garcia G, Kliszewski S, et al. The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of patients with small cell lung cancer and non-small cell lung cancer. J Carcinog. 2006;5:4.PubMedCentralPubMedCrossRef
23.
Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res. 2006;4(2):130–7.PubMedCentralPubMedCrossRef
24.
Chiriva-Internati M, Ferrari R, Prabhakar M, Yu Y, Baggoni L, Moreno J, et al. The pituitary tumor transforming gene 1 (PTTG-1): an immunological target for multiple myeloma. J Transl Med. 2008;6:15.PubMedCentralPubMedCrossRef
25.
Wang Z, Lu QY, Chen P, Zhang P, Cong YQ. Expression of pituitary tumor-transforming gene in patients with multiple myeloma. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006;14(6):1143–5.PubMed
26.
Dominguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, et al. hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene. 1998;17(17):2187–93.PubMedCrossRef
27.
Asosingh K, Radl J, Van Riet I, Van Camp B, Vanderkerken K. The 5TMM series: a useful in vivo mouse model of human multiple myeloma. Hematol J. 2000;1(5):351–6.PubMedCrossRef
28.
Dallas SL, Garrett IR, Oyajobi BO, Dallas MR, Boyce BF, Bauss F, et al. Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease. Blood. 1999;93(5):1697–706.PubMed
29.
Kassambara A, Schoenhals M, Moreaux J, Veyrune JL, Reme T, Goldschmidt H, et al. Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells. PLoS One. 2013;8(4):e62752.PubMedCentralPubMedCrossRef
30.
Kakar SS. Molecular cloning, genomic organization, and identification of the promoter for the human pituitary tumor transforming gene (PTTG). Gene. 1999;240(2):317–24.PubMedCrossRef
31.
Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, et al. Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1999;13(1):156–66.PubMedCrossRef
32.
33.
Salehi F, Kovacs K, Scheithauer BW, Lloyd RV, Cusimano M. Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. Endocr Relat Cancer. 2008;15(3):721–43.PubMedCrossRef
34.
Saez C, Pereda T, Borrero JJ, Espina A, Romero F, Tortolero M, et al. Expression of hpttg proto-oncogene in lymphoid neoplasias. Oncogene. 2002;21(53):8173–7.PubMedCrossRef
35.
Chung TH, Mulligan G, Fonseca R, Chng WJ. A novel measure of chromosome instability can account for prognostic difference in multiple myeloma. PLoS One. 2013;8(6):e66361.PubMedCentralPubMedCrossRef
36.
Bernal JA, Luna R, Espina A, Lazaro I, Ramos-Morales F, Romero F, et al. Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis. Nat Genet. 2002;32(2):306–11.PubMedCrossRef
37.
Zou H, McGarry TJ, Bernal T, Kirschner MW. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science. 1999;285(5426):418–22.PubMedCrossRef
38.
Kim D, Pemberton H, Stratford AL, Buelaert K, Watkinson JC, Lopes V, et al. Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells. Oncogene. 2005;24(30):4861–6.PubMedCrossRef
39.
Winnepenninckx V, Debiec-Rychter M, Belien JA, Fiten P, Michiels S, Lazar V, et al. Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma. Mod Pathol. 2006;19(9):1170–80.PubMedCrossRef
40.
Yu R, Heaney AP, Lu W, Chen J, Melmed S. Pituitary tumor transforming gene causes aneuploidy and p53-dependent and p53-independent apoptosis. J Biol Chem. 2000;275(47):36502–5.PubMedCrossRef
41.
Yu R, Lu W, Chen J, McCabe CJ, Melmed S. Overexpressed pituitary tumor-transforming gene causes aneuploidy in live human cells. Endocrinology. 2003;144(11):4991–8.PubMedCrossRef
42.
Jallepalli PV, Waizenegger IC, Bunz F, Langer S, Speicher MR, Peters JM, et al. Securin is required for chromosomal stability in human cells. Cell. 2001;105(4):445–57.PubMedCrossRef
43.
Mu YM, Oba K, Yanase T, Ito T, Ashida K, Goto K, et al. Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21(WAF1/CIP1). Endocr J. 2003;50(6):771–81.PubMedCrossRef
44.
Heaney AP, Nelson V, Fernando M, Horwitz G. Transforming events in thyroid tumorigenesis and their association with follicular lesions. J Clin Endocrinol Metab. 2001;86(10):5025–32.PubMedCrossRef
45.
Hose D, Reme T, Hielscher T, Moreaux J, Messner T, Seckinger A, et al. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma. Haematologica. 2011;96(1):87–95.PubMedCentralPubMedCrossRef
46.
Ramos-Morales F, Dominguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, et al. Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product. Oncogene. 2000;19(3):403–9.PubMedCrossRef
47.
Filippella M, Galland F, Kujas M, Young J, Faggiano A, Lombardi G, et al. Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol (Oxf). 2006;65(4):536–43.CrossRef
48.
Menicanin D, Bartold PM, Zannettino AC, Gronthos S. Identification of a common gene expression signature associated with immature clonal mesenchymal cell populations derived from bone marrow and dental tissues. Stem Cells Dev. 2010;19(10):1501–10.PubMedCrossRef
49.
Yu R, Ren SG, Horwitz GA, Wang Z, Melmed S. Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: evidence from live cell imaging. Mol Endocrinol. 2000;14(8):1137–46.PubMedCrossRef
50.
Yu R, Cruz-Soto M, Li Calzi S, Hui H, Melmed S. Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells. J Endocrinol. 2006;191(1):45–53.PubMedCrossRef
51.
Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1997;11(4):433–41.PubMedCrossRef
52.
Ishitsuka Y, Kawachi Y, Taguchi S, Maruyama H, Fujisawa Y, Furuta J, et al. Pituitary tumor-transforming gene 1 enhances proliferation and suppresses early differentiation of keratinocytes. J Invest Dermatol. 2012;132(7):1775–84.PubMedCrossRef
53.
Chesnokova V, Kovacs K, Castro AV, Zonis S, Melmed S. Pituitary hypoplasia in Pttg-/- mice is protective for Rb+/- pituitary tumorigenesis. Mol Endocrinol. 2005;19(9):2371–9.PubMedCentralPubMedCrossRef
54.
Cho-Rok J, Yoo J, Jang YJ, Kim S, Chu IS, Yeom YI, et al. Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell growth in vitro and in vivo. Hepatology. 2006;43(5):1042–52.PubMedCrossRef
55.
Genkai N, Homma J, Sano M, Tanaka R, Yamanaka R. Increased expression of pituitary tumor-transforming gene (PTTG)-1 is correlated with poor prognosis in glioma patients. Oncol Rep. 2006;15(6):1569–74.PubMed
56.
Tfelt-Hansen J, Yano S, Bandyopadhyay S, Carroll R, Brown EM, Chattopadhyay N. Expression of pituitary tumor transforming gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells: function and regulation of PTTG in U87 astrocytoma cells. Endocrinology. 2004;145(9):4222–31.PubMedCrossRef
57.
Rubinek T, Chesnokova V, Wolf I, Wawrowsky K, Vlotides G, Melmed S. Discordant proliferation and differentiation in pituitary tumor-transforming gene-null bone marrow stem cells. Am J Physiol Cell Physiol. 2007;293(3):C1082–92.PubMedCrossRef
58.
Tong Y, Tan Y, Zhou C, Melmed S. Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition. Oncogene. 2007;26(38):5596–605.PubMedCentralPubMedCrossRef
59.
60.
Kuiper R, Broyl A, de Knegt Y, van Vliet M, van Beers E, van der Holt B, et al. A gene expression signature for high-risk multiple myeloma. Leukemia. 2012;26(11):2406-2413.
61.
Chng WJ, Kumar S, Vanwier S, Ahmann G, Price-Troska T, Henderson K, et al. Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling. Cancer Res. 2007;67(7):2982–9.PubMedCrossRef
62.
Romagnoli M, Seveno C, Wuilleme-Toumi S, Amiot M, Bataille R, Minvielle S, et al. The imbalance between Survivin and Bim mediates tumour growth and correlates with poor survival in patients with multiple myeloma. Br J Haematol. 2009;145(2):180–9.PubMedCrossRef
63.
Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy Jr J. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106(1):296–303.PubMedCentralPubMedCrossRef
64.
Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998;396(6711):580–4.PubMedCrossRef
65.
Pines J, Hunter T. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. Cell. 1989;58(5):833–46.PubMedCrossRef
66.
Romagnoli M, Trichet V, David C, Clement M, Moreau P, Bataille R, et al. Significant impact of survivin on myeloma cell growth. Leukemia. 2007;21(5):1070–8.PubMed
67.
68.
Badie C, Bourhis J, Sobczak-Thepot J, Haddada H, Chiron M, Janicot M, et al. p53-dependent G2 arrest associated with a decrease in cyclins A2 and B1 levels in a human carcinoma cell line. Br J Cancer. 2000;82(3):642–50.PubMedCentralPubMedCrossRef
69.
Taylor WR, Schonthal AH, Galante J, Stark GR. p130/E2F4 binds to and represses the cdc2 promoter in response to p53. J Biol Chem. 2001;276(3):1998–2006.PubMedCrossRef
70.
Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem. 2002;277(5):3247–57.PubMedCrossRef
71.
Lode L, Eveillard M, Trichet V, Soussi T, Wuilleme S, Richebourg S, et al. Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma. Haematologica. 2010;95(11):1973–6.PubMedCentralPubMedCrossRef
72.
Neri A, Baldini L, Trecca D, Cro L, Polli E, Maiolo AT. p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy. Blood. 1993;81(1):128–35.PubMed
73.
Corradini P, Inghirami G, Astolfi M, Ladetto M, Voena C, Ballerini P, et al. Inactivation of tumor suppressor genes, p53 and Rb1, in plasma cell dyscrasias. Leukemia. 1994;8(5):758–67.PubMed
74.
Chang H, Qi C, Yi QL, Reece D, Stewart AK. p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood. 2005;105(1):358–60.PubMedCrossRef
75.
Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, Iwakawa R, et al. Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res. 2012;72(1):100–11.PubMedCrossRef
76.
Kretschmer C, Sterner-Kock A, Siedentopf F, Schoenegg W, Schlag PM, Kemmner W. Identification of early molecular markers for breast cancer. Mol Cancer. 2011;10(1):15.PubMedCentralPubMedCrossRef
77.
Kanehira M, Harada Y, Takata R, Shuin T, Miki T, Fujioka T, et al. Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis. Oncogene. 2007;26(44):6448–55.PubMedCrossRef
78.
Harada Y, Kanehira M, Fujisawa Y, Takata R, Shuin T, Miki T, et al. Cell-permeable peptide DEPDC1-ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells. Cancer Res. 2010;70(14):5829–39.PubMedCrossRef
79.
Shah PP, Fong MY, Kakar SS. PTTG induces EMT through integrin alphaVbeta3-focal adhesion kinase signaling in lung cancer cells. Oncogene. 2012;31(26):3124–35.PubMedCentralPubMedCrossRef
80.
Shah PP, Kakar SS. Pituitary tumor transforming gene induces epithelial to mesenchymal transition by regulation of Twist, Snail, Slug, and E-cadherin. Cancer Lett. 2011;311(1):66–76.PubMedCentralPubMedCrossRef
81.
Yoon CH, Kim MJ, Lee H, Kim RK, Lim EJ, Yoo KC, et al. PTTG1 oncogene promotes tumor malignancy via epithelial to mesenchymal transition and expansion of cancer stem cell population. J Biol Chem. 2012;287(23):19516–27.PubMedCentralPubMedCrossRef
82.
Azab AK, Hu J, Quang P, Azab F, Pitsillides C, Awwad R, et al. Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features. Blood. 2012;119(24):5782–94.PubMedCentralPubMedCrossRef
83.
Ishikawa H, Heaney AP, Yu R, Horwitz GA, Melmed S. Human pituitary tumor-transforming gene induces angiogenesis. J Clin Endocrinol Metab. 2001;86(2):867–74.PubMed
84.
McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, et al. Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors. J Clin Endocrinol Metab. 2002;87(9):4238–44.PubMedCrossRef
85.
Giatromanolaki A, Bai M, Margaritis D, Bourantas KL, Koukourakis MI, Sivridis E, et al. Hypoxia and activated VEGF/receptor pathway in multiple myeloma. Anticancer Res. 2010;30(7):2831–6.PubMed
86.
Gupta D, Treon SP, Shima Y, Hideshima T, Podar K, Tai YT, et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia. 2001;15(12):1950–61.PubMedCrossRef
87.
Sato N, Hattori Y, Wenlin D, Yamada T, Kamata T, Kakimoto T, et al. Elevated level of plasma basic fibroblast growth factor in multiple myeloma correlates with increased disease activity. Jpn J Cancer Res. 2002;93(4):459–66.PubMedCrossRef
88.
Agnelli L, Mosca L, Fabris S, Lionetti M, Andronache A, Kwee I, et al. A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect. Genes Chromosomes Cancer. 2009;48(7):603–14.PubMedCrossRef
89.
Reme T, Hose D, Theillet C, Klein B. Modeling risk stratification in human cancer. Bioinformatics. 2013;29(9):1149–57.PubMedCrossRef
90.
Broyl A, Hose D, Lokhorst H, de Knegt Y, Peeters J, Jauch A, et al. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood. 2010;116(14):2543–53.PubMedCrossRef
91.
Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467–72.PubMedCentralPubMedCrossRef
92.
Gautier L, Cope L, Bolstad BM, Irizarry RA. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307–15.PubMedCrossRef
93.
Dennis Jr G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4(5):3.CrossRef
94.
da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.CrossRef
95.
Schweitzer KM, Vicart P, Delouis C, Paulin D, Drager AM, Langenhuijsen MM, et al. Characterization of a newly established human bone marrow endothelial cell line: distinct adhesive properties for hematopoietic progenitors compared with human umbilical vein endothelial cells. Lab Invest. 1997;76(1):25–36.PubMed
96.
Diamond P, Labrinidis A, Martin SK, Farrugia AN, Gronthos S, To LB, et al. Targeted disruption of the CXCL12/CXCR4 axis inhibits osteolysis in a murine model of myeloma-associated bone loss. J Bone Miner Res. 2009;24(7):1150–61.PubMedCrossRef
97.
Cheong CM, Chow AW, Fitter S, Hewett DR, Martin SK, Williams SA, et al. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo. Exp Cell Res. 2015;332(1):24–38.PubMedCrossRef
98.
Diril MK, Ratnacaram CK, Padmakumar VC, Du T, Wasser M, Coppola V, et al. Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc Natl Acad Sci U S A. 2012;109(10):3826–31.PubMedCentralPubMedCrossRef
99.
Lei W, Feng XH, Deng WB, Ni H, Zhang ZR, Jia B, et al. Progesterone and DNA damage encourage uterine cell proliferation and decidualization through up-regulating ribonucleotide reductase 2 expression during early pregnancy in mice. J Biol Chem. 2012;287(19):15174–92.PubMedCentralPubMedCrossRef
100.
Mrozik KM, Cheong CM, Hewett D, Chow AW, Blaschuk OW, Zannettino AC et al. Therapeutic targeting of N-cadherin is an effective treatment for multiple myeloma. Br J Haematol. 2015
101.
Zinonos I, Luo KW, Labrinidis A, Liapis V, Hay S, Panagopoulos V, et al. Pharmacologic inhibition of bone resorption prevents cancer-induced osteolysis but enhances soft tissue metastasis in a mouse model of osteolytic breast cancer. Int J Oncol. 2014;45(2):532–40.PubMedCentralPubMed
102.
Martin SK, Gan ZY, Fitter S, To LB, Zannettino AC. The effect of the PI3K inhibitor BKM120 on tumour growth and osteolytic bone disease in multiple myeloma. Leuk Res. 2015;39(3):380–7.PubMedCrossRef
103.
Gan ZY, Fitter S, Vandyke K, To LB, Zannettino AC, Martin SK. The effect of the dual PI3K and mTOR inhibitor BEZ235 on tumour growth and osteolytic bone disease in multiple myeloma. Eur J Haematol. 2015;94(4):343–54.PubMedCrossRef
Metadata
Title
PTTG1 expression is associated with hyperproliferative disease and poor prognosis in multiple myeloma
Authors
Jacqueline E. Noll
Kate Vandyke
Duncan R. Hewett
Krzysztof M. Mrozik
Rachel J. Bala
Sharon A. Williams
Chung H. Kok
Andrew CW Zannettino
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0209-2

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
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