Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

BMC Cancer

Volumn 12, Issue , 2012, Pages

  Dimberg, Lina Y ^a   Dimberg, Anna ^a   Ivarsson, Karolina ^a   Fryknäs, Mårten ^a,b   Rickardson, Linda ^b   Tobin, Gerard ^a   Ekman, Simon ^a   Larsson, Rolf ^b   Gullberg, Urban ^c   Nilsson, Kenneth ^a   Öberg, Fredrik ^a   Wiklund, Helena J ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b UPPSALA UNIVERSITY   (Sweden)

^c LUND UNIVERSITY   (Sweden)

Author keywords

Apoptosis; Drug sensitivity; Hematopoetic malignancies; IFN; Multiple myeloma; Stat1; Stat3

Indexed keywords

BORTEZOMIB; DEXAMETHASONE; DOXORUBICIN; ETOPOSIDE; FAS ANTIGEN; FLUDARABINE; GELDANAMYCIN; INTERFERON REGULATORY FACTOR 1; INTERLEUKIN 6; MESSENGER RNA; PROTEIN BCL 2; PROTEIN MCL 1; PROTEIN NOXA; RESAZURIN; STAT1 PROTEIN; STAT3 PROTEIN; THALIDOMIDE; VORINOSTAT;

APOPTOSIS; ARTICLE; ATTENUATION; BCL 2 GENE; CANCER CELL CULTURE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DISEASE ASSOCIATION; DRUG SENSITIZATION; GENE; GENE EXPRESSION REGULATION; HARAKIRI GENE; HIGH THROUGHPUT SCREENING; IC 50; MCL 1 GENE; MULTIPLE MYELOMA; MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION; NOXA GENE; NUCLEAR LOCALIZATION SIGNAL; OUTCOME ASSESSMENT; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SEQUENCE ANALYSIS; TRANSCRIPTION INITIATION; UPREGULATION;

ACTIVE TRANSPORT, CELL NUCLEUS; ANTIGENS, CD95; APOPTOSIS; CELL LINE, TUMOR; CELL NUCLEUS; CLUSTER ANALYSIS; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTERLEUKIN-6; MULTIPLE MYELOMA; STAT1 TRANSCRIPTION FACTOR; STAT3 TRANSCRIPTION FACTOR; TRANSCRIPTION, GENETIC;

EID: 84864271417     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-12-318     Document Type: Article

References (50)

1. Mahindra A, Laubach J, Raje N, Munshi N, Richardson PG, Anderson K. Latest advances and current challenges in the treatment of multiple myeloma. Nat Rev Clin Oncol 2012, 9:135-143. 10.1038/nrclinonc.2012.15, 22349016.
2. Jernberg-Wiklund H, Nilsson K. Targeting the IGF-1R signaling and mechanisms for epigenetic gene silencing in human multiple myeloma. Ups J Med Sci 2012, 117:166-177. 10.3109/03009734.2012.659293, 3339548, 22348393.
3. Darnell JE. STATs and gene regulation. Science 1997, 277:1630-1635. 10.1126/science.277.5332.1630, 9287210.
4. Smithgall TE, Briggs SD, Schreiner S, Lerner EC, Cheng H, Wilson MB. Control of myeloid differentiation and survival by Stats. Oncogene 2000, 19:2612-2618. 10.1038/sj.onc.1203477, 10851060.
5. Bowman T, Garcia R, Turkson J, Jove R. STATs in oncogenesis. Oncogene 2000, 19:2474-2488. 10.1038/sj.onc.1203527, 10851046.
6. Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999, 10:105-115. 10.1016/S1074-7613(00)80011-4, 10023775.
7. Bharti AC, Shishodia S, Reuben JM, Weber D, Alexanian R, Raj-Vadhan S, Estrov Z, Talpaz M, Aggarwal BB. Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood 2004, 103:3175-3184. 10.1182/blood-2003-06-2151, 15070700.
8. Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 1998, 334(Pt 2):297-314. 1219691, 9716487.
9. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE. Stat3 as an oncogene. Cell 1999, 98:295-303. 10.1016/S0092-8674(00)81959-5, 10458605.
10. Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 2002, 8:945-954.
11. Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, Fu XY. Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science 1996, 272:719-722. 10.1126/science.272.5262.719, 8614832.
12. Kumar A, Commane M, Flickinger TW, Horvath CM, Stark GR. Defective TNF-alpha-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases. Science 1997, 278:1630-1632. 10.1126/science.278.5343.1630, 9374464.
13. Lee KY, Anderson E, Madani K, Rosen GD. Loss of STAT1 expression confers resistance to IFN-gamma-induced apoptosis in ME180 cells. FEBS Lett 1999, 459:323-326. 10.1016/S0014-5793(99)01283-1, 10526158.
14. Stephanou A, Brar BK, Scarabelli TM, Jonassen AK, Yellon DM, Marber MS, Knight RA, Latchman DS. Ischemia-induced STAT-1 expression and activation play a critical role in cardiomyocyte apoptosis. J Biol Chem 2000, 275:10002-10008. 10.1074/jbc.275.14.10002, 10744676.
15. Bauer K, Kretzschmar AK, Cvijic H, Blumert C, Loffler D, Brocke-Heidrich K, Schiene-Fischer C, Fischer G, Sinz A, Clevenger CV, Horn F. Cyclophilins contribute to Stat3 signaling and survival of multiple myeloma cells. Oncogene 2009, 28:2784-2795. 10.1038/onc.2009.142, 19503092.
16. Qing Y, Stark GR. Alternative activation of STAT1 and STAT3 in response to interferon-gamma. J Biol Chem 2004, 279:41679-41685. 10.1074/jbc.M406413200, 15284232.
17. Costa-Pereira AP, Tininini S, Strobl B, Alonzi T, Schlaak JF, Is'harc H, Gesualdo I, Newman SJ, Kerr IM, Poli V. Mutational switch of an IL-6 response to an interferon-gamma-like response. Proc Natl Acad Sci U S A 2002, 99:8043-8047. 10.1073/pnas.122236099, 123017, 12060750.
18. Stephanou A, Brar BK, Knight RA, Latchman DS. Opposing actions of STAT-1 and STAT-3 on the Bcl-2 and Bcl-x promoters. Cell Death Differ 2000, 7:329-330. 10.1038/sj.cdd.4400656, 10866494.
19. Page BD, Ball DP, Gunning PT. Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin Ther Pat 2011, 21:65-83. 10.1517/13543776.2011.539205, 21114420.
20. Souissi I, Ladam P, Cognet JA, Le Coquil S, Varin-Blank N, Baran-Marszak F, Metelev V, Fagard R. A STAT3-inhibitory hairpin decoy oligodeoxynucleotide discriminates between STAT1 and STAT3 and induces death in a human colon carcinoma cell line. Mol Cancer 2012, 11:12. 10.1186/1476-4598-11-12, 3325846, 22423663.
21. Spets H, Georgii-Hemming P, Siljason J, Nilsson K, Jernberg-Wiklund H. Fas/APO-1 (CD95)-mediated apoptosis is activated by interferon-gamma and interferon- in interleukin-6 (IL-6)-dependent and IL-6-independent multiple myeloma cell lines. Blood 1998, 92:2914-2923.
22. Dimberg LY, Dimberg AI, Ivarsson K, Stromberg T, Osterborg A, Nilsson K, Oberg F, Jernberg Wiklund H. Ectopic and IFN-induced expression of Fas overcomes resistance to Fas-mediated apoptosis in multiple myeloma cells. Blood 2005, 106:1346-1354. 10.1182/blood-2004-04-1322, 15860671.
23. Sironi JJ, Ouchi T. STAT1-induced apoptosis is mediated by caspases 2, 3, and 7. J Biol Chem 2004, 279:4066-4074.
24. Jernberg-Wiklund H, Pettersson M, Carlsson M, Nilsson K. Increase in interleukin 6 (IL-6) and IL-6 receptor expression in a human multiple myeloma cell line, U-266, during long-term in vitro culture and the development of a possible autocrine IL-6 loop. Leukemia 1992, 6:310-318.
25. Muller M, Laxton C, Briscoe J, Schindler C, Improta T, Darnell JE, Stark GR, Kerr IM. Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways. Embo J 1993, 12:4221-4228. 413716, 7693454.
26. Dimberg A, Nilsson K, Oberg F. Phosphorylation-deficient Stat1 inhibits retinoic acid-induced differentiation and cell cycle arrest in U-937 monoblasts. Blood 2000, 96:2870-2878.
27. Andrews NC, Faller DV. A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res 1991, 19:2499. 10.1093/nar/19.9.2499, 329467, 2041787.
28. Lew DJ, Decker T, Strehlow I, Darnell JE. Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. Mol Cell Biol 1991, 11:182-191. 359608, 1898761.
29. Nilsson E, Lendahl U. Transient expression of a human beta-actin promoter/lacZ gene introduced into mouse embryos correlates with a low degree of methylation. Mol Reprod Dev 1993, 34:149-157. 10.1002/mrd.1080340206, 7680211.
30. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 2002, 30:e57. 10.1093/nar/gnf056, 117299, 12060695.
31. Eldering E, Spek CA, Aberson HL, Grummels A, Derks IA, de Vos AF, McElgunn CJ, Schouten JP. Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways. Nucleic Acids Res 2003, 31:e153. 10.1093/nar/gng153, 290288, 14627843.
32. O'Brien J, Wilson I, Orton T, Pognan F. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 2000, 267:5421-5426. 10.1046/j.1432-1327.2000.01606.x, 10951200.
33. Pagé B, Pagé M, Noel C. A new fluorometric assay for cytotoxicity measurements in vitro. Int J Oncol 1993, 3:473-476.
34. Larsson R, Kristensen J, Sandberg C, Nygren P. Laboratory determination of chemotherapeutic drug resistance in tumor cells from patients with leukemia, using a fluorometric microculture cytotoxicity assay (FMCA). Int J Cancer 1992, 50:177-185. 10.1002/ijc.2910500204, 1730510.
35. Rickardson L, Fryknas M, Haglund C, Lovborg H, Nygren P, Gustafsson MG, Isaksson A, Larsson R. Screening of an annotated compound library for drug activity in a resistant myeloma cell line. Cancer Chemother Pharmacol 2006, 58:749-758. 10.1007/s00280-006-0216-7, 16528529.
36. Alas S, Bonavida B. Inhibition of Constitutive STAT3 Activity Sensitizes Resistant Non-Hodgkin's Lymphoma and Multiple Myeloma to Chemotherapeutic Drug-mediated Apoptosis. Clin Cancer Res 2003, 9:316-326.
37. De Vos J, Jourdan M, Tarte K, Jasmin C, Klein B. JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells. Br J Haematol 2000, 109:823-828. 10.1046/j.1365-2141.2000.02127.x, 10929036.
38. Ihle JN. The Stat family in cytokine signaling. Curr Opin Cell Biol 2001, 13:211-217. 10.1016/S0955-0674(00)00199-X, 11248555.
39. Stephanou A, Latchman DS. Opposing actions of STAT-1 and STAT-3. Growth Factors 2005, 23:177-182. 10.1080/08977190500178745, 16243709.
40. Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian Z, Nguyen VA, Gao B. Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. J Clin Invest 2002, 110:1503-1513. 151811, 12438448.
41. Scarabelli TM, Townsend PA, Chen-Scarabelli C, Yuan Z, McCauley RB, Di Rezze J, Patel D, Putt J, Allebban Z, Abboud J, et al. Amino acid supplementation differentially modulates STAT1 and STAT3 activation in the myocardium exposed to ischemia/reperfusion injury. Am J Cardiol 2008, 101:63E-68E.
42. Thyrell L, Arulampalam V, Hjortsberg L, Farnebo M, Grander D. Pokrovskaja Tamm K: Interferon alpha induces cell death through interference with interleukin 6 signaling and inhibition of STAT3 activity. Exp Cell Res 2007, 313:4015-4024. 10.1016/j.yexcr.2007.08.007, 17880940.
43. Bromberg JF. Activation of STAT proteins and growth control. Bioessays 2001, 23:161-169. 10.1002/1521-1878(200102)23:2<161::AID-BIES1023>3.0.CO;2-0, 11169589.
44. Le Gouill S, Podar K, Harousseau JL, Anderson KC. Mcl-1 regulation and its role in multiple myeloma. Cell Cycle 2004, 3:1259-1262. 10.4161/cc.3.10.1196, 15467463.
45. Derenne S, Monia B, Dean NM, Taylor JK, Rapp MJ, Harousseau JL, Bataille R, Amiot M. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood 2002, 100:194-199. 10.1182/blood.V100.1.194, 12070027.
46. Inohara N, Ding L, Chen S, Nunez G. harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). Embo J 1997, 16:1686-1694. 10.1093/emboj/16.7.1686, 1169772, 9130713.
47. Townsend PA, Scarabelli TM, Davidson SM, Knight RA, Latchman DS, Stephanou A. STAT-1 interacts with p53 to enhance DNA damage-induced apoptosis. J Biol Chem 2004, 279:5811-5820.
48. Shibue T, Takeda K, Oda E, Tanaka H, Murasawa H, Takaoka A, Morishita Y, Akira S, Taniguchi T, Tanaka N. Integral role of Noxa in p53-mediated apoptotic response. Genes Dev 2003, 17:2233-2238. 10.1101/gad.1103603, 196460, 12952892.
49. Fryknas M, Dhar S, Oberg F, Rickardson L, Rydaker M, Goransson H, Gustafsson M, Pettersson U, Nygren P, Larsson R, Isaksson A. STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines. Int J Cancer 2007, 120:189-195. 10.1002/ijc.22291, 17072862.
50. Khodarev NN, Beckett M, Labay E, Darga T, Roizman B, Weichselbaum RR. STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells. Proc Natl Acad Sci U S A 2004, 101:1714-1719. 10.1073/pnas.0308102100, 341831, 14755057.