Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase

Journal of Biological Chemistry

Volumn 287, Issue 16, 2012, Pages 13228-13238

  Montalvo Ortiz, Brenda L ^a   Castillo Pichardo, Linette ^a,c   Hernández, Eliud ^b   Humphries Bickley, Tessa ^a   De La Mota Peynado, Alina ^c   Cubano, Luis A ^c   Vlaar, Cornelis P ^b,d   Dharmawardhane, Suranganie ^a,d  

^a UNIVERSITY OF PUERTO RICO SCHOOL OF MEDICINE   (Puerto Rico)

^b UNIVERSITY OF PUERTO RICO   (Puerto Rico)

^c SCHOOL OF MEDICINE   (Puerto Rico)

^d NONE   (Puerto Rico)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; CELL MEMBRANES; NUCLEOTIDES; PROTEINS;

BREAST CANCER CELLS; EFFECTIVE CONCENTRATION; GUANINE NUCLEOTIDE EXCHANGE FACTORS; MAMMARY EPITHELIAL CELLS; METASTATIC CANCER CELLS; METASTATIC CANCERS; P-21 ACTIVATED KINASE; SMALL MOLECULE INHIBITOR;

DISEASES;

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; EHOP 016; ENZYME INHIBITOR; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; P21 ACTIVATED KINASE 1; PROTEIN CDC42; RAC PROTEIN; RAC1 PROTEIN; RAC3 PROTEIN; UNCLASSIFIED DRUG; VAV2 PROTEIN;

ARTICLE; BINDING AFFINITY; BREAST CANCER; BREAST EPITHELIUM; CANCER CELL; CELL MIGRATION; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENCY; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG SYNTHESIS; EPITHELIUM CELL; HUMAN; HUMAN CELL; IC 50; LAMELLIPODIUM; METASTASIS; PRIORITY JOURNAL; PROTEIN EXPRESSION;

EID: 84859768464     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.334524     Document Type: Article

References (87)

1. Ridley, A. J. (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 16, 522-529
2. Mack, N. A., Whalley, H. J., Castillo-Lluva, S., and Malliri, A. (2011) The diverse roles of Rac signaling in tumorigenesis. Cell Cycle 10, 1571-1581
3. Lazer, G., and Katzav, S. (2011) Guanine nucleotide exchange factors for RhoGTPases. Good therapeutic targets for cancer therapy? Cell. Signal. 23, 969-979
4. Parri, M., and Chiarugi, P. (2010) Rac and Rho GTPases in cancer cell motility control. Cell Commun. Signal. 8, 23
5. Mulloy, J. C., Cancelas, J. A., Filippi, M. D., Kalfa, T. A., Guo, F., and Zheng, Y. (2010) Rho GTPases in hematopoiesis and hemopathies. Blood 115, 936-947
6. Pai, S. Y., Kim, C., and Williams, D. A. (2010) Rac GTPases in human diseases. Dis. Markers 29, 177-187
7. Vega, F. M., and Ridley, A. J. (2008) Rho GTPases in cancer cell biology. FEBS Lett. 582, 2093-2101
8. Tang, Y., Olufemi, L., Wang, M. T., and Nie, D. (2008) Role of Rho GTPases in breast cancer. Front. Biosci. 13, 759-776 (Pubitemid 351599780)
9. Karlsson, R., Pedersen, E. D., Wang, Z., and Brakebusch, C. (2009) Rho GTPase function in tumorigenesis. Biochim. Biophys. Acta 1796, 91-98
10. Hall, A. (2005) Rho GTPases and the control of cell behavior. Biochem. Soc. Trans. 33, 891-895
11. Lin, M., and van Golen, K. L. (2004) Rho-regulatory proteins in breast cancer cell motility and invasion. Breast Cancer Res. Treat. 84, 49-60 (Pubitemid 38388860)
12. Kleer, C. G., Griffith, K. A., Sabel, M. S., Gallagher, G., van Golen, K. L., Wu, Z. F., and Merajver, S. D. (2005) RhoC-GTPase is a novel tissue biomarker associated with biologically aggressive carcinomas of the breast. Breast Cancer Res. Treat. 93, 101-110 (Pubitemid 41396771)
13. Chan, A. Y., Coniglio, S. J., Chuang, Y. Y., Michaelson, D., Knaus, U. G., Philips, M. R., and Symons, M. (2005) Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion. Oncogene 24, 7821-7829 (Pubitemid 41715188)
14. Burbelo, P., Wellstein, A., and Pestell, R. G. (2004) Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res. Treat. 84, 43-48 (Pubitemid 38388859)
15. Qiu, R. G., Chen, J., Kirn, D., McCormick, F., and Symons, M. (1995) An essential role for Rac in Ras transformation. Nature 374, 457-459
16. Renshaw, M. W., Lea-Chou, E., and Wang, J. Y. (1996) Rac is required for v-Abl tyrosine kinase to activate mitogenesis. Curr. Biol. 6, 76-83 (Pubitemid 126663442)
17. Azios, N. G., Krishnamoorthy, L., Harris, M., Cubano, L. A., Cammer, M., and Dharmawardhane, S. F. (2007) Estrogen and resveratrol regulate Rac and Cdc42 signaling to the actin cytoskeleton of metastatic breast cancer cells. Neoplasia 9, 147-158
18. Baugher, P. J., Krishnamoorthy, L., Price, J. E., and Dharmawardhane, S. F. (2005) Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells. Breast Cancer Res. 7, R965-R974
19. Mira, J. P., Benard, V., Groffen, J., Sanders, L. C., and Knaus, U. G. (2000) Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc. Natl. Acad. Sci. U.S.A. 97, 185-189 (Pubitemid 30055805)
20. 1 cell cycle arrest or apoptosis in breast cancer cells through down-regulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein. Mol. Cancer Ther. 9, 1657-1668
21. Schnelzer, A., Prechtel, D., Knaus, U., Dehne, K., Gerhard, M., Graeff, H., Harbeck, N., Schmitt, M., and Lengyel, E. (2000) Rac1 in human breast cancer. overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene 19, 3013-3020
22. Saci, A., Cantley, L. C., and Carpenter, C. L. (2011) Rac1 regulates the activity ofmTORC1andmTORC2and controls cellular size. Mol. Cell 42, 50-61
23. Gulhati, P., Bowen, K. A., Liu, J., Stevens, P. D., Rychahou, P. G., Chen, M., Lee, E. Y., Weiss, H. L., O'Connor, K. L., Gao, T., and Evers, B. M. (2011) mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res. 71, 3246-3256
24. Dokmanovic, M., Hirsch, D. S., Shen, Y., and Wu, W. J. (2009) Rac1 contributes to trastuzumab resistance of breast cancer cells. Rac1 as a potential therapeutic target for the treatment of trastuzumab-resistant breast cancer. Mol. Cancer Ther. 8, 1557-1569
25. Rosenblatt, A. E., Garcia, M. I., Lyons, L., Xie, Y., Maiorino, C., Désiré, L., Slingerland, J., and Burnstein, K. L. (2011) Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer. Endocr. Relat. Cancer 18, 207-219
26. Singh, A., Karnoub, A. E., Palmby, T. R., Lengyel, E., Sondek, J., and Der, C. J. (2004) Rac1b, a tumor-associated, constitutively active Rac1 splice variant, promotes cellular transformation. Oncogene 23, 9369-9380 (Pubitemid 40069669)
27. Stallings-Mann, M., and Radisky, D. (2007) Matrix metalloproteinase- induced malignancy in mammary epithelial cells. Cells Tissues Organs 185, 104-110 (Pubitemid 46956850)
28. Jordan, P., Brazåo, R., Boavida, M. G., Gespach, C., and Chastre, E. (1999) Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene 18, 6835-6839
29. Matos, P., and Jordan, P. (2008) Increased Rac1b expression sustains colorectal tumor cell survival. Mol. Cancer Res. 6, 1178-1184
30. Whale, A., Hashim, F. N., Fram, S., Jones, G. E., and Wells, C. M. (2011) Signaling to cancer cell invasion through PAK family kinases. Front. Biosci. 16, 849-864
31. Dummler, B., Ohshiro, K., Kumar, R., and Field, J. (2009) Pak protein kinases and their role in cancer. Cancer Metastasis Rev. 28, 51-63
32. Kichina, J. V., Goc, A., Al-Husein, B., Somanath, P. R., and Kandel, E. S. (2010) PAK1 as a therapeutic target. Expert Opin. Ther. Targets 14, 703-725
33. Yi, C., Maksimoska, J., Marmorstein, R., and Kissil, J. L. (2010) Development of small-molecule inhibitors of the group I p21-activated kinases, emerging therapeutic targets in cancer. Biochem. Pharmacol. 80, 683-689
34. Bishop, A. L., and Hall, A. (2000) Rho GTPases and their effector proteins. Biochem. J. 348, 241-255 (Pubitemid 30345195)
35. Baranwal, S., and Alahari, S. K. (2011) Curr. Drug Targets 12, 1194-1201
36. Deacon, S. W., and Peterson, J. R. (2008) Chemical inhibition through conformational stabilization of Rho GTPase effectors. Handb. Exp. Pharmacol. 186, 431-460
37. Jaffe, A. B., and Hall, A. (2005) Rho GTPases. Biochemistry and biology. Annu. Rev. Cell Dev. Biol. 21, 247-269
38. Rossman, K. L., Der, C. J., and Sondek, J. (2005) GEF means go. Turning on RHO GTPases with guanine nucleotide exchange factors. Nat. Rev. Mol. Cell Biol. 6, 167-180 (Pubitemid 40215811)
39. Schmidt, A., and Hall, A. (2002) Guanine nucleotide exchange factors for Rho GTPases. Turning on the switch. Genes Dev. 16, 1587-1609 (Pubitemid 34743321)
40. Bernards, A. (2003) GAPs galore! A survey of putative Ras superfamily GTPase-activating proteins in man and Drosophila. Biochim. Biophys. Acta 1603, 47-82
41. Palmby, T. R., Abe, K., Karnoub, A. E., and Der, C. J. (2004) Vav transformation requires activation of multiple GTPases and regulation of gene expression. Mol. Cancer Res. 2, 702-711
42. Miller, S. L., DeMaria, J. E., Freier, D. O., Riegel, A. M., and Clevenger, C. V. (2005) Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor. Mol. Endocrinol. 19, 939-949 (Pubitemid 40397058)
43. Sastry, S. K., Rajfur, Z., Liu, B. P., Cote, J. F., Tremblay, M. L., and Burridge, K. (2006) PTP-PEST couples membrane protrusion and tail retraction via VAV2 and p190RhoGAP. J. Biol. Chem. 281, 11627-11636 (Pubitemid 43855420)
44. Minard, M. E., Kim, L. S., Price, J. E., and Gallick, G. E. (2004) The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion, and tumor progression. Breast Cancer Res. Treat. 84, 21-32 (Pubitemid 38388857)
45. Brantley-Sieders, D. M., Zhuang, G., Vaught, D., Freeman, T., Hwang, Y., Hicks, D., and Chen, J. (2009) Host deficiency in Vav2/3 guanine nucleotide exchange factors impairs tumor growth, survival, and angiogenesis in vivo. Mol. Cancer Res. 7, 615-623
46. Zugaza, J. L., López-Lago, M. A., Caloca, M. J., Dosil, M., Movilla, N., and Bustelo, X. R. (2002) Structural determinants for the biological activity of Vav proteins. J. Biol. Chem. 277, 45377-45392 (Pubitemid 36159146)
47. Liu, B. P., and Burridge, K. (2000) Vav2 activates Rac1, Cdc42, and RhoA downstream from growth factor receptors but not β1 integrins. Mol. Cell Biol. 20, 7160-7169
48. Gao, Y., Dickerson, J. B., Guo, F., Zheng, J., and Zheng, Y. (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc. Natl. Acad. Sci. U.S.A. 101, 7618-7623 (Pubitemid 38658078)
49. Chrencik, J. E., Brooun, A., Zhang, H., Mathews, I. I., Hura, G. L., Foster, S. A., Perry, J. J., Streiff, M., Ramage, P., Widmer, H., Bokoch, G. M., Tainer, J. A., Weckbecker, G., and Kuhn, P. (2008) Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1. J. Mol. Biol. 380, 828-843
50. Abe, K., Rossman, K. L., Liu, B., Ritola, K. D., Chiang, D., Campbell, S. L., Burridge, K., and Der, C. J. (2000) Vav2 is an activator of Cdc42, Rac1, and RhoA. J. Biol. Chem. 275, 10141-10149 (Pubitemid 30202067)
51. Sosa, M. S., Lopez-Haber, C., Yang, C., Wang, H., Lemmon, M. A., Busillo, J. M., Luo, J., Benovic, J. L., Klein-Szanto, A., Yagi, H., Gutkind, J. S., Parsons, R. E., and Kazanietz, M. G. (2010) Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Mol. Cell 40, 877-892
52. Montero, J. C., Seoane, S., Ocaña, A., and Pandiella, A. (2011) P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer. Oncogene 30, 1059-1071
53. Thomas, E. K., Cancelas, J. A., Chae, H. D., Cox, A. D., Keller, P. J., Perrotti, D., Neviani, P., Druker, B. J., Setchell, K. D., Zheng, Y., Harris, C. E., and Williams, D. A. (2007) Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell 12, 467-478 (Pubitemid 350046406)
54. Binker, M. G., Binker-Cosen, A. A., Gaisano, H. Y., and Cosen-Binker, L. I. (2008) Inhibition of Rac1 decreases the severity of pancreatitis and pancreatitis- associated lung injury in mice. Exp. Physiol. 93, 1091-1103
55. Akbar, H., Cancelas, J., Williams, D. A., Zheng, J., and Zheng, Y. (2006) Rational design and applications of a Rac GTPase-specific small molecule inhibitor. Methods Enzymol. 406, 554-565 (Pubitemid 43207468)
56. Nassar, N., Cancelas, J., Zheng, J., Williams, D. A., and Zheng, Y. (2006) Structure-function-based design of small molecule inhibitors targeting Rho family GTPases. Curr. Top. Med. Chem. 6, 1109-1116 (Pubitemid 44110923)
57. Hernández, E., De La Mota-Peynado, A., Dharmawardhane, S., and Vlaar, C. P. (2010) Novel inhibitors of Rac1 in metastatic breast cancer. P. R. Health Sci. J. 29, 348-356
58. Onesto, C., Shutes, A., Picard, V., Schweighoffer, F., and Der, C. J. (2008) Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Methods Enzymol. 439, 111-129
59. Shutes, A., Onesto, C., Picard, V., Leblond, B., Schweighoffer, F., and Der, C. J. (2007) Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J. Biol. Chem. 282, 35666-35678 (Pubitemid 350277149)
60. Ferri, N., Corsini, A., Bottino, P., Clerici, F., and Contini, A. (2009) Virtual screening approach for the identification of new Rac1 inhibitors. J. Med. Chem. 52, 4087-4090
61. Beausoleil, E., Chauvignac, C., Taverne, T., Lacombe, S., Pognante, L., Leblond, B., Pallares, D., Oliveira, C. D., Bachelot, F., Carton, R., Peillon, H., Coutadeur, S., Picard, V., Lambeng, N., Désiré, L., and Schweighoffer, F. (2009) Structure-activity relationship of isoform-selective inhibitors of Rac1/1b GTPase nucleotide binding. Bioorg. Med. Chem. Lett. 19, 5594-5598
62. Bouquier, N., Vignal, E., Charrasse, S., Weill, M., Schmidt, S., Léonetti, J. P., Blangy, A., and Fort, P. (2009) A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway. Chem. Biol. 16, 657-666
63. Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., and Olson, A. J. (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19, 1639-1662 (Pubitemid 128590223)
64. Huey, R., Morris, G. M., Olsen, A. J., and Goodsell, D. S. (2007) A semiempirical free energy force field with charge-based desolvation. J. Comput. Chem. 28, 1145-1152 (Pubitemid 46506716)
65. Zheng, Y., Nassar, N., and Skowronek, K. R. (2010) United States Patent 17,826,982
66. García-Mata, R., Wennerberg, K., Arthur, W. T., Noren, N. K., Ellerbroek, S. M., and Burridge, K. (2006) Analysis of activated GAPs and GEFs in cell lysates. Methods Enzymol. 406, 425-437 (Pubitemid 43207456)
67. Worthylake, D. K., Rossman, K. L., and Sondek, J. (2000) Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature 408, 682-688 (Pubitemid 32015977)
68. Rapley, J., Tybulewicz, V. L., and Rittinger, K. (2008) Crucial structural role for the PH and C1 domains of the Vav1 exchange factor. EMBO Rep. 9, 655-661 (Pubitemid 351927686)
69. Garrett, T. A., Van Buul, J. D., and Burridge, K. (2007) VEGF-induced Rac1 activation in endothelial cells is regulated by the guanine nucleotide exchange factor Vav2. Exp. Cell Res. 313, 3285-3297 (Pubitemid 47284065)
70. Karnoub, A. E., Worthylake, D. K., Rossman, K. L., Pruitt, W. M., Campbell, S. L., Sondek, J., and Der, C. J. (2001) Molecular basis for Rac1 recognition by guanine nucleotide exchange factors. Nat. Struct. Biol. 8, 1037-1041 (Pubitemid 33101623)
71. Fukata, M., Nakagawa, M., and Kaibuchi, K. (2003) Roles of Rho-family GTPases in cell polarization and directional migration. Curr. Opin. Cell Biol. 15, 590-597 (Pubitemid 37176968)
72. Dharmawardhane, S., Schürmann, A., Sells, M. A., Chernoff, J., Schmid, S. L., and Bokoch, G. M. (2000) Regulation of macropinocytosis by p21- activated kinase-1. Mol. Biol. Cell 11, 3341-3352
73. Sun, D., Xu, D., and Zhang, B. (2006) Rac signaling in tumorigenesis and as target for anticancer drug development. Drug Resist. Updat. 9, 274-287 (Pubitemid 46357635)
74. Yamazaki, D., Kurisu, S., and Takenawa, T. (2005) Regulation of cancer cell motility through actin reorganization. Cancer Sci. 96, 379-386 (Pubitemid 41179738)
75. 56 of Rac1 specifies interaction with a subset of guanine nucleotide exchange factors. J. Biol. Chem. 276, 47530-47541
76. Servitja, J. M., Marinissen, M. J., Sodhi, A., Bustelo, X. R., and Gutkind, J. S. (2003) Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src. J. Biol. Chem. 278, 34339-34346 (Pubitemid 37553278)
77. Patel, V., Rosenfeldt, H. M., Lyons, R., Servitja, J. M., Bustelo, X. R., Siroff, M., and Gutkind, J. S. (2007) Persistent activation of Rac1 in squamous carcinomas of the head and neck. Evidence for an EGFR/Vav2 signaling axis involved in cell invasion. Carcinogenesis 28, 1145-1152
78. Movilla, N., Dosil, M., Zheng, Y., and Bustelo, X. R. (2001) How Vav proteins discriminate the GTPases Rac1 and RhoA from Cdc42. Oncogene 20, 8057-8065 (Pubitemid 34028330)
79. Duan, L., Chen, G., Virmani, S., Ying, G., Raja, S. M., Chung, B. M., Rainey, M. A., Dimri, M., Ortega-Cava, C. F., Zhao, X., Clubb, R. J., Tu, C., Reddi, A. L., Naramura, M., Band, V., and Band, H. (2010) Distinct roles for Rho versus Rac/Cdc42 GTPases downstream of Vav2 in regulating mammary epithelial acinar architecture. J. Biol. Chem. 285, 1555-1568
80. Murga, C., Zohar, M., Teramoto, H., and Gutkind, J. S. (2002) Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-κB. Oncogene 21, 207-216 (Pubitemid 34102129)
81. Nethe, M., Anthony, E. C., Fernandez-Borja, M., Dee, R., Geerts, D., Hensbergen, P. J., Deelder, A. M., Schmidt, G., and Hordijk, P. L. (2010) Focaladhesion targeting links caveolin-1 to a Rac1 degradation pathway. J. Cell Sci. 123, 1948-1958
82. Chan, A., Akhtar, M., Brenner, M., Zheng, Y., Gulko, P. S., and Symons, M. (2007) The GTPase Rac regulates the proliferation and invasion of fibroblast- like synoviocytes from rheumatoid arthritis patients. Mol. Med. 13, 297-304 (Pubitemid 47175039)
83. Kirui, J. K., Xie, Y., Wolff, D. W., Jiang, H., Abel, P. W., and Tu, Y. (2010) Gβγ signaling promotes breast cancer cell migration and invasion. J. Pharmacol. Exp. Ther. 333, 393-403
84. Han, G., Fan, B., Zhang, Y., Zhou, X., Wang, Y., Dong, H., Wei, Y., Sun, S., Hu, M., Zhang, J., and Wei, L. (2008) Positive regulation of migration and invasion by vasodilator-stimulated phosphoprotein via Rac1 pathway in human breast cancer cells. Oncol. Rep. 20, 929-939
85. Shi, H. Y., Stafford, L. J., Liu, Z., Liu, M., and Zhang, M. (2007) Maspin controls mammary tumor cell migration through inhibiting Rac1 and Cdc42, but not the RhoA GTPase. Cell Motil. Cytoskeleton 64, 338-346 (Pubitemid 46608668)
86. Sala, G., Dituri, F., Raimondi, C., Previdi, S., Maffucci, T., Mazzoletti, M., Rossi, C., Iezzi, M., Lattanzio, R., Piantelli, M., Iacobelli, S., Broggini, M., and Falasca, M. (2008) Phospholipase Cγ1 is required for metastasis development and progression. Cancer Res. 68, 10187-10196
87. Schunke, D., Span, P., Ronneburg, H., Dittmer, A., Vetter, M., Holzhausen, H. J., Kantelhardt, E., Krenkel, S., Müller, V., Sweep, F. C., Thomssen, C., and Dittmer, J. (2007) Cyclooxygenase-2 is a target gene of Rho GDP dissociation inhibitor β in breast cancer cells. Cancer Res. 67, 10694-10702 (Pubitemid 350145895)