Targeting PIM kinase enhances the activity of sunitinib in renal cell carcinoma

British Journal of Cancer

Volumn 105, Issue 10, 2011, Pages 1563-1573

  Mahalingam, D ^a   Espitia, C M ^a   Medina, E C ^a   Esquivel, J A ^a   Kelly, K R ^a   Bearss, D ^b   Choy, G ^b   Taverna, P ^b   Carew, J S ^a   Giles, F J ^a   Nawrocki, S T ^a  

^a CTRC Institute for Drug Development   (United States)

^b SuperGen Inc   (United States)

Author keywords

c Myc; PIM; renal cell carcinoma; SGI 1776; sunitinib

Indexed keywords

PROTEIN KINASE INHIBITOR; PROTEIN KINASE PIM 1; SGI 1176; SUNITINIB; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL VIABILITY; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG SENSITIVITY; DRUG TARGETING; DRUG TOLERABILITY; ENZYME INHIBITION; EXPERIMENTAL NEOPLASM; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE IDENTIFICATION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IN VIVO STUDY; KIDNEY CARCINOMA; MOUSE; NONHUMAN; ONCOGENE C MYC; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TUMOR VOLUME; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; CELL LINE, TUMOR; FEMALE; HUMANS; IMIDAZOLES; IMMUNOHISTOCHEMISTRY; INDOLES; KIDNEY NEOPLASMS; MICE; MICE, INBRED BALB C; MICE, NUDE; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MYC; PROTO-ONCOGENE PROTEINS C-PIM-1; PYRIDAZINES; PYRROLES; REAL-TIME POLYMERASE CHAIN REACTION;

EID: 80755136604     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2011.426     Document Type: Article

References (50)

1. Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM (2003a) SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2(5): 471-478
2. Abrams TJ, Murray LJ, Pesenti E, Holway VW, Colombo T, Lee LB, Cherrington JM, Pryer NK (2003b) Preclinical evaluation of the tyrosine kinase inhibitor SU11248 as a single agent and in combination with 'standard of care' therapeutic agents for the treatment of breast cancer. Mol Cancer Ther 2(10): 1011-1021
3. Adam M, Pogacic V, Bendit M, Chappuis R, Nawijn MC, Duyster J, Fox CJ, Thompson CB, Cools J, Schwaller J (2006) Targeting PIM kinases impairs survival of hematopoietic cells transformed by kinase inhibitor-sensitive and kinase inhibitor-resistant forms of Fms-like tyrosine kinase 3 and BCR/ABL. Cancer Res 66(7): 3828-3835
4. Aho TL, Sandholm J, Peltola KJ, Mankonen HP, Lilly M, Koskinen PJ (2004) Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site. FEBS Lett 571(1-3): 43-49 (Pubitemid 38992921)
5. Amaravadi R, Thompson CB (2005) The survival kinases Akt and Pim as potential pharmacological targets. J Clin Invest 115(10): 2618-2624 (Pubitemid 41434384)
6. Beharry Z, Zemskova M, Mahajan S, Zhang F, Ma J, Xia Z, Lilly M, Smith CD, Kraft AS (2009) Novel benzylidene-thiazolidine-2,4-diones inhibit Pim protein kinase activity and induce cell cycle arrest in leukemia and prostate cancer cells. Mol Cancer Ther 8(6): 1473-1483
7. Beier UH, Weise JB, Laudien M, Sauerwein H, Gorogh T (2007) Overexpression of Pim-1 in head and neck squamous cell carcinomas. Int J Oncol 30(6): 1381-1387
8. Carew JS, Medina EC, Esquivel II JA, Mahalingam D, Swords R, Kelly K, Zhang H, Huang P, Mita AC, Mita MM, Giles FJ, Nawrocki ST (2009) Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J Cell Mol Med 14(10): 2448-2459
9. Chen J, Kobayashi M, Darmanin S, Qiao Y, Gully C, Zhao R, Yeung SC, Lee MH (2009a) Pim-1 plays a pivotal role in hypoxia-induced chemoresistance. Oncogene 28(28): 2581-2592
10. Chen JL, Limnander A, Rothman PB (2008) Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. Blood 111(3): 1677-1685 (Pubitemid 351213459)
11. Chen LS, Redkar S, Bearss D, Wierda WG, Gandhi V (2009b) Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood 114(19): 4150-4157
12. Cibull TL, Jones TD, Li L, Eble JN, Ann Baldridge L, Malott SR, Luo Y, Cheng L (2006) Overexpression of Pim-1 during progression of prostatic adenocarcinoma. J Clin Pathol 59(3): 285-288 (Pubitemid 43344891)
13. Eichmann A, Yuan L, Breant C, Alitalo K, Koskinen PJ (2000) Developmental expression of pim kinases suggests functions also outside of the hematopoietic system. Oncogene 19(9): 1215-1224 (Pubitemid 30157552)
14. Fox CJ, Hammerman PS, Cinalli RM, Master SR, Chodosh LA, Thompson CB (2003) The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor. Genes Dev 17(15): 1841-1854 (Pubitemid 36944562)
15. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC (2007a) HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 11(4): 335-347 (Pubitemid 46518312)
16. Gordan JD, Lal P, Dondeti VR, Letrero R, Parekh KN, Oquendo CE, Greenberg RA, Flaherty KT, Rathmell WK, Keith B, Simon MC, Nathanson KL (2008) HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell 14(6): 435-446
17. Gordan JD, Thompson CB, Simon MC (2007b) HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 12(2): 108-113 (Pubitemid 47199124)
18. Heng DY, Bukowski RM (2008) Anti-angiogenic targets in the treatment of advanced renal cell carcinoma. Curr Cancer Drug Targets 8(8): 676-682
19. Hogan C, Hutchison C, Marcar L, Milne D, Saville M, Goodlad J, Kernohan N, Meek D (2008) Elevated levels of oncogenic protein kinase Pim-1 induce the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma. J Biol Chem 283(26): 18012-18023
20. Hu XF, Li J, Vandervalk S, Wang Z, Magnuson NS, Xing PX (2009) PIM-1-specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis. J Clin Invest 119(2): 362-375
21. Iliopoulos O, Levy AP, Jiang C, Kaelin Jr WG, Goldberg MA (1996) Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci USA 93(20): 10595-10599 (Pubitemid 26333032)
22. Kaelin Jr WG (2007) The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res 13(2 Pt 2): 680s-684s
23. Kaelin Jr WG (2008) Kidney cancer: now available in a new flavor. Cancer Cell 14(6): 423-424
24. Kelly KR, Espitia CM, Taverna P, Choy G, Padmanabhan S, Nawrocki ST, Giles FJ, Carew JS (2011) Targeting PIM kinase activity significantly augments the efficacy of cytarabine. Br J Haematol; e-pub ahead of print 21 June 2011
25. Li YY, Popivanova BK, Nagai Y, Ishikura H, Fujii C, Mukaida N (2006) Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines. Cancer Res 66(13): 6741-6747 (Pubitemid 44085632)
26. Mahalingam D, Medina EC, Esquivel II JA, Espitia CM, Smith S, Oberheu K, Swords R, Kelly KR, Mita MM, Mita AC, Carew JS, Giles FJ, Nawrocki ST (2010) Vorinostat enhances the activity of temsirolimus in renal cell carcinoma through suppression of survivin levels. Clin Cancer Res 16(1): 141-153
27. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9(1): 327-337 (Pubitemid 36109749)
28. Mochizuki T, Kitanaka C, Noguchi K, Muramatsu T, Asai A, Kuchino Y (1999) Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway. J Biol Chem 274(26): 18659-18666
29. Morishita D, Katayama R, Sekimizu K, Tsuruo T, Fujita N (2008) Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res 68(13): 5076-5085
30. Moroy T, Verbeek S, Ma A, Achacoso P, Berns A, Alt F (1991) E mu N-and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice. Oncogene 6(11): 1941-1948 (Pubitemid 21924031)
31. Mumenthaler SM, Ng PY, Hodge A, Bearss D, Berk G, Kanekal S, Redkar S, Taverna P, Agus DB, Jain A (2009) Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther 8(10): 2882-2893
32. Nawrocki ST, Carew JS, Maclean KH, Courage JF, Huang P, Houghton JA, Cleveland JL, Giles FJ, McConkey DJ (2008) Myc regulates aggresome formation, the induction of Noxa, and apoptosis in response to the combination of bortezomib and SAHA. Blood 112(7): 2917-2926
33. Nilsson JA, Cleveland JL (2003) Myc pathways provoking cell suicide and cancer. Oncogene 22(56): 9007-9021 (Pubitemid 38121701)
34. Nishioka C, Ikezoe T, Yang J, Yokoyama A (2009) Sunitinib, an orally available receptor tyrosine kinase inhibitor, induces monocytic differentiation of acute myelogenous leukemia cells that is enhanced by 1,25-dihydroxy-vitamin D(3). Leukemia 23(11): 2171-2173
35. Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2(7): 423-427
36. Pelengaris S, Khan M, Evan G (2002) c-MYC: more than just a matter of life and death. Nat Rev Cancer 2(10): 764-776 (Pubitemid 37328911)
37. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9): e45
38. Popivanova BK, Li YY, Zheng H, Omura K, Fujii C, Tsuneyama K, Mukaida N (2007) Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis. Cancer Sci 98(3): 321-328 (Pubitemid 46195601)
39. Seandel M, Shia J, Linkov I, Maki RG, Antonescu CR, Dupont J (2006) The activity of sunitinib against gastrointestinal stromal tumor seems to be distinct from its antiangiogenic effects. Clin Cancer Res 12(20 Pt 1): 6203-6204 (Pubitemid 44703787)
40. Sosman JA, Puzanov I, Atkins MB (2007) Opportunities and obstacles to combination targeted therapy in renal cell cancer. Clin Cancer Res 13(2 Pt 2): 764s-769s
41. Tang SW, Chang WH, Su YC, Chen YC, Lai YH, Wu PT, Hsu CI, Lin WC, Lai MK, Lin JY (2009) MYC pathway is activated in clear cell renal cell carcinoma and essential for proliferation of clear cell renal cell carcinoma cells. Cancer Lett 273(1): 35-43
42. Turner KJ, Moore JW, Jones A, Taylor CF, Cuthbert-Heavens D, Han C, Leek RD, Gatter KC, Maxwell PH, Ratcliffe PJ, Cranston D, Harris AL (2002) Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res 62(10): 2957-2961 (Pubitemid 34525785)
43. Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, Double JA, Everitt J, Farningham DA, Glennie MJ, Kelland LR, Robinson V, Stratford IJ, Tozer GM, Watson S, Wedge SR, Eccles SA (2010) Guidelines for the welfare and use of animals in cancer research. Br J Cancer 102(11): 1555-1577
44. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H (2009) Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res 69(6): 2506-2513
45. Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ, Lilly M (2003) The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. J Biol Chem 278(46): 45358-45367 (Pubitemid 37432672)
46. Zemskova M, Sahakian E, Bashkirova S, Lilly M (2008) The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells. J Biol Chem 283(30): 20635-20644
47. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL (2007a) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11(5): 407-420 (Pubitemid 46670080)
48. Zhang Y, Wang Z, Li X, Magnuson NS (2008) Pim kinase-dependent inhibition of c-Myc degradation. Oncogene 27(35): 4809-4819
49. Zhang Y, Wang Z, Magnuson NS (2007b) Pim-1 kinase-dependent phosphorylation of p21Cip1/WAF1 regulates its stability and cellular localization in H1299 cells. Mol Cancer Res 5(9): 909-922 (Pubitemid 47416668)
50. Zippo A, De Robertis A, Serafini R, Oliviero S (2007) PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat Cell Biol 9(8): 932-944 (Pubitemid 47190448)